Do medicine residents triage patients with gastrointestinal bleeding appropriately?

Background: Gastrointestinal specialists depend on internal medicine (IM) teams to accurately identify acute gastrointestinal bleeding (GIB). We evaluated whether IM residents’ assessment of GIB correlated with the impressions of GI specialists during consultations at an inner-city university teaching hospital. Methods: A questionnaire was distributed to house staff requesting GIB consultations and to the GI fellows performing the consults between August 2011 and April 2012. Residents and fellows were asked to assess GIB, specifically melena, using a stool color card and digital rectal examination (DRE) findings. Fellow DRE findings served as controls for stool color identification. Results: Eighty-seven GI consults were eligible for the study. Residents and fellows completed 81 and 86 questionnaires, respectively. A total of 76 questionnaires were included for analysis. A DRE was performed by medical staff before calling a consult in 65% of cases compared with fellows (97% of cases, P = 0.0001). Residents more frequently labeled stool as melena (42%) in patients as compared with fellows (12%, P = 0.0001). Residents inaccurately identified melenic stools in 22 patients (11 based on stool color and 11 based on DRE findings). Residents were more likely to label a consult as emergent than fellows (13.5% vs 4%, P < 0.05). Conclusion: Residents are less likely to perform DRE during an evaluation for GIB and to accurately identify melena based on stool color or DRE findings. There appears to be a need to educate residents on the appropriate terminology for stool color and the importance of DRE to accurately triage patients with acute GIBs.     

Amplification of genes encoding human myeloid membrane antigens after DNA-mediated gene transfer

Spontaneous amplification of genes encoding two different human myeloid surface antigens was observed after DNA-mediated gene transfer of cellular DNA from the human myeloid cell line HL-60 into NIH-3T3 mouse fibroblasts. Transformed recipient cells with highly amplified expression of either of two donor membrane polypeptides, gp150 or p67, were isolated with a fluorescence-activated cell sorter (FACS), using monoclonal antibodies specific for human myeloid cells. Immunoprecipitation of enzymatically radioiodinated polypeptides from the surface of transformed NIH-3T3 cells confirmed that expression of these proteins was amplified tenfold to 20-fold in comparison to their expression on human myeloid cell lines. The cellular DNA of cloned secondary and tertiary transformants expressing high levels of gp150 and p67 contained amplified sets of DNA restriction fragments that hybridized with human repetitive DNA sequences. Cytogenetic analysis of subclones overexpressing gp150 revealed extrachromosomal double minutes (DMs), whose presence correlated with the unstable expression of the membrane polypeptide. Human sequences in gp150-positive clones did not localize to chromosomes, consistent with their association with extrachromosomal DMs. By contrast, p67-positive subclones stably expressed the antigen, and in situ hybridization to metaphase spreads demonstrated that amplified human DNA sequences were integrated into a specific marker chromosome. Cytogenetic analysis of the parental NIH- 3T3 subclone used in these studies disclosed DMs in a low percentage of metaphases, suggesting that the recipient cells have a propensity for amplifying donor DNA.     

Volumetric Changes in Apical Radiolucencies of Endodontically Treated Teeth Assessed by Cone-beam Computed Tomography 1 Year after Orthograde Retreatment

Introduction

Cone-beam computed tomography (CBCT) allows us to assess in 3 dimensions the location and size of periapical radiolucencies. We aimed to assess by CBCT scans the volumetric changes of periapical radiolucencies in endodontically treated teeth 1 year after orthograde retreatment.

Methods

Forty-five root-filled teeth with persistent apical periodontitis requiring endodontic orthograde retreatment from 37 individuals were included in the study. The research protocol was approved by the VU University Medical Center Amsterdam ethics committee (2007/265), and the participants signed a letter of consent. We made 2 CBCT scans for every patient, the first one before retreatment and the second one a year later. Two observers measured independently the volume of radiolucencies on CBCT images by using the AMIRA software. The intraclass correlation coefficient was used to evaluate interobserver agreement, and the Wilcoxon signed rank test was used to assess pretreatment and post-treatment volume size.

Results

The intraclass correlation coefficients were 0.994 and 0.998 for the scans before retreatment and 1 year after, respectively. The recall rate was 78% for the teeth and 73% for the patients. The volumetric change in periapical radiolucencies 1 year after retreatment was statistically significant (z = −3.112, P < .005). The volume of periapical radiolucencies reduced in 20 teeth (57%), remained unchanged in 8 (23%), and increased in 7 (20%).

Conclusions

One year after endodontic orthograde retreatment, the volume of periapical radiolucencies reduced significantly in 57% of the teeth.     

A systematic review of the results of surgery and radiotherapy on tumor control for pediatric craniopharyngioma

Objective

Craniopharyngiomas are rare tumors with bimodal incidence in the pediatric and adult age groups. Treatment strategies range from aggressive resection to planned limited resection combined with adjuvant therapies. Currently there is no consensus for standard of care for pediatric craniopharyngioma.

Materials and methods

We performed a systematic review of the published literature on pediatric craniopharyngioma. Patients were grouped based on extent of resection into gross total resection (GTR), subtotal resection (STR), and biopsy procedures. These groups were compared with respect to tumor control. Chi square was used to compare rates of recurrence. Kaplan–Meier was used to generate progression-free survival (PFS) estimates. Cox proportional hazard modeling was used to evaluate risk of progression. Each extent of resection group was also subdivided based on adjuvant therapy and compared.

Results

A total of 109 studies described extent of resection resulting in a cohort of 531 patients. Recurrence data were available for 377 patients. There was no difference in 1- or 5-year PFS between the groups who underwent GTR and STR combined with radiation (XRT; log-rank; p?=?0.76; 1-year PFS 89 vs 84 %; 5-year PFS 77 vs 73 %, respectively). One-year PFS was 84 % for STR+XRT compared to 76 % for STR alone while 5-year PFS was 73 % for STR+XRT compared to 43 % for STR alone (log-rank; p?=?0.003).

Conclusion

Although there are limitations of a systematic review of retrospective data, our results suggest that STR+XRT of pediatric craniopharyngioma is associated with similar rates of tumor control as GTR.     

Activation-induced cytidine deaminase induces DNA break repair events more frequently in the Ig switch region than other sites in the mammalian genome

Activation-induced cytidine deaminase (AID) produces DNA breaks in immunoglobulin genes during antibody diversification. Double-stranded breaks (DSB) in the switch region mediate class switch recombination, and contribute to gene conversion and somatic hypermutation in the variable regions. However, the relative extent to which AID induces DSB in these regions or between these and other actively expressed sequences is unknown. Here, we exploited an enhancer-trap plasmid that identifies DSB in actively expressed loci to investigate the frequency and position of AID-induced vector integration events in mouse hybridoma cells. Compared to control cells, wild-type AID stimulates plasmid integration into the genome by as much as 29-fold. Southern and digestion-circularization PCR analysis revealed non-uniformity in the integration sites, with biases of 30- and 116-fold for the immunoglobulin kappa light chain and mu heavy chain genes, respectively. Further, within the immunoglobulin mu gene, 73% of vector integrations map to the mu switch region, an enhancement of five- and 12-fold compared to the adjacent heavy chain variable and mu gene constant regions, respectively. Thus, among potential highly transcribed genes in mouse hybridoma cells, the immunoglobulin heavy and light chain genes are important AID targets, with the immunoglobulin mu switch region being preferred compared to other genomic sites.     

Advanced Gynecologic Laparoscopy in a Fast-Track Ambulatory Surgery Center

Background/Objectives:

It has been shown that major gynecologic laparoscopy is safe in hospital ambulatory settings, but there is little data to suggest the same in freestanding ambulatory surgery centers. This study evaluates the safety and efficacy of advanced gynecologic laparoscopic surgery using a fast-track model in freestanding ambulatory surgery centers and discusses our institution protocols.

Methods:

Retrospective, multicenter review was conducted of major gynecologic surgeries from August 1^st 2010 to September 30^th 2011 in 3 surgical centers with one primary surgeon. All patients were treated for symptomatic uterine leiomyomas and/or endometriosis. Primary outcome measures were unplanned admissions and discharge within 23 hours.

Results:

One hundred and thirty-four patients underwent major laparoscopic gynecologic surgery with a total of 160 procedures: 77 stage IV endometriosis treatment including 7 disk excisions of endometriosis from the large bowel, 3 ureteroneocystostomies and 1 partial bladder resection, 38 myomectomies, and 34 hysterectomies including 12 modified radical hysterectomies. The overall unplanned admission rate was 4.5%. One hundred and thirty-one patients (97.7%) were discharged within 24 hours after surgery. Three patients (2.2%) were transferred to the hospital postoperatively: 1 patient for observation of postoperative anemia and 2 patients for postoperative fever. Three patients (2.2%) were admitted to the hospital after discharge: 1 patient for postoperative ileus, 1 patient for postoperative fever, and 1 patient with septic pelvic thrombophlebitis. These postoperative issues all resolved without complication, and all patients had an uneventful follow-up.

Conclusions:

With appropriate resources and an experienced surgeon, advanced laparoscopic surgery can be safely performed in a fast-track ambulatory surgery center with a high rate of discharge within 23 hours and low unplanned readmission rate.     

Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine

In vivo observations on the kinetics of F cells and of fetal hemoglobin (HbF) synthesis and in vitro studies of erythroid progenitors, their number, and the gamma-gene expression in their progeny were carried out in baboons (Papio cynocephalus) treated with 5-azacytidine. Maximum effect on the increase of HbF production in vivo was observed only when an expanded erythroid marrow population was present. In these animals, as well as in normal animals, treatment resulted in a significant reduction of the late erythroid progenitor cell pools (erythroid clusters and erythroid colony-forming units, CFU-E) in the marrow. This reduction was more pronounced among those progenitors grown in the absence of added erythropoietin, and it was followed by a rebound a few days after treatment cessation, reflecting the accumulation of regenerating progenitors. An early increase in the in vitro synthesis of HbF in erythroid clusters and CFU-E colonies was observed. This increase was further documented at the cellular level, with immunofluorescent labeling of colonies with monoclonal anti-gamma- globin chain antibodies. In contrast to the findings in late progenitors, the number of erythroid burst-forming unit (BFU-E) colonies and the synthesis of HbF in these colonies was not influenced significantly by 5-azacytidine treatment. It is proposed that the toxic effects of 5-azacytidine on late progenitors, leading to faster mobilization of earlier progenitors to the next more mature compartment, play a role in the in vivo augmentation of HbF synthesis by this drug. This perturbation in the progenitor cell population kinetics and the presumed hypomethylation of the surviving differentiating cells may act synergistically to produce a maximum HbF response after 5-azacytidine treatment.     

6q deletions define distinct clinico-pathologic subsets of non- Hodgkin's lymphoma

Commonly observed in lymphoid neoplasms, deletions of 6q have been correlated with histologic and clinical subsets of non-Hodgkin's lymphoma (NHL). Our recent analysis of loss of heterozygosity of 6q loci in NHL showed two regions of minimal molecular deletion (RMD), an RMD1 at 6q25-27 and an RMD2 at 6q21-23. To establish correlations between these RMDs and regions of minimal cytogenetic deletions (RCDs) on 6q, and to define associations between RCDs and clinico-pathologic features, we have analyzed chromosome 6 abnormalities in 459 consecutively ascertained, karyotypically abnormal cases of NHL. Among these, 126 (27.5%) cases had structural abnormalities of chromosome 6, of which 94 were deletions. Analysis of these deletions identified three RCDs. An RCD1 encompassing 6q25-27 was seen in 45 intermediate- grade NHL. An RCD2 at 6q21 was observed in 11 high-grade NHL, 9 of which were of the immunoblastic subtype. An RCD3 at 6q23 was noted in 18 low-grade NHL lacking a t(14;18) translocation. Of these 18 cases, 12 were small lymphocytic NHL and, in 2 of these, del(6q) was the sole karyotypic abnormality. In 20 cases of low-grade NHL with t(14;18), the deletions spanned both RCD1 and RCD3. These data suggested the presence of at least 3 tumor suppressor genes on 6q within RCD1, RCD2, and RCD3; they also showed associations between RCDs in 6q and subsets of NHL, including a specific association between a group of well-differentiated lymphoid neoplasms and RCD3. The apparent heterogeneity of breakpoints when all NHLs are considered together explains the inability of previous studies to reliably establish correlations between recurring 6q deletions and histologic and clinical features of NHL.