Controversies in cardiovascular care: silent myocardial ischemia

The objective evidence of silent myocardial ischemia--ischemia in the absence of classical chest pain--includes ST-segment shifts (usually depression), momentary left ventricular failure, and perfusion defects on scintigraphic studies. Assessment of angina patients with 24-hour ambulatory monitoring may uncover episodes of silent ischemia, the existence of which may give important information regarding prognosis and may help structure a more effective therapeutic regimen. The emerging recognition of silent ischemia as a significant clinical entity may eventually result in an expansion of current therapy--not only to ameliorate chest pain, but to minimize or eliminate ischemia in the absence of chest pain.     

Bone morphogenic protein-2 signaling in human disc degeneration and correlation to the Pfirrmann MRI grading system

BACKGROUND CONTEXTBack and neck pain secondary to disc degeneration is a major public health burden. There is a need for therapeutic treatments to restore intervertebral disc (IVD) composition and function.PURPOSETo quantify ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens collected from patients undergoing surgery for disc degeneration, to correlate ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression in IVD specimens to the 5-level Pfirrmann MRI grading system, and to compare ALK3, BMP-2, pSMAD1/5/8 and MMP-13 expression between cervical and lumbar degenerative disc specimens.STUDY DESIGNAn immunohistochemical study assessing ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in human control and degenerative IVD specimens.METHODSHuman IVD specimens were collected from surgical patients who underwent discectomy and interbody fusion at our institution between 1/2015 and 8/2017. Each patient underwent MRI prior to surgery. The degree of disc degeneration was measured according to the 5-level Pfirrmann MRI grading system. Patients were categorized into either the 1) control group (Pfirrmann grades I-II) or 2) degenerative group (Pfirrmann grades III-V). Histology slides of the collected IVD specimens were prepared and immunohistochemical staining was performed to assess ALK3, BMP-2, pSMAD1/5/8, and MMP-13 expression levels in the control and degenerative specimens. Expression levels were also correlated to the Pfirrmann criteria. Lastly, the degenerative specimens were stratified according to their vertebral level and expression levels between the degenerative lumbar and cervical discs were compared.RESULTSFifty-two patients were enrolled; however, 2 control and 2 degenerative patients were excluded due to incomplete data sets. Of the remaining 48 patients, there were 12 control and 36 degenerative specimens. Degenerative specimens had increased expression levels of BMP-2 (p=.0006) and pSMAD1/5/8 (p<.0001). Pfirrmann grade 3 (p=.0365) and grade 4 (p=.0008) discs had significantly higher BMP-2 expression as compared to grade 2 discs. Pfirrmann grade 4 discs had higher pSMAD1/5/8 expression as compared to grade 2 discs (p<.0001). There were no differences in ALK3 or MMP-13 expression between the control and degenerative discs (p>.05). Stratifying the degenerative specimens according to their vertebral level showed no significant differences in expression levels between the lumbar and cervical discs (p>.05).CONCLUSIONSBMP-2 and pSMAD1/5/8 signaling activity was significantly upregulated in the human degenerative specimens, while ALK3 and MMP-13 expression were not significantly changed. The expression levels of BMP-2 and pSMAD1/5/8 correlate positively with the degree of disc degeneration measured according to the Pfirrmann MRI grading system.CLINICAL SIGNIFICANCEBMP-SMAD signaling represents a promising therapeutic target to restore IVD composition and function in the setting of disc degeneration.     

A Novel Telemedicine System for Care of Statewide Hand Trauma

Background: Telemedicine is an evolving tool to increase patients’ access to subspecialty care. Since 2014, Arkansas has been utilizing telemedicine in the evaluation of patients with hand injuries. The purpose of this study is to assess the effect of this novel telemedicine system for the management of hand trauma on patient transfer. Methods: We reviewed data from the first year of the telemedicine program (2014) and compared it to data from the year prior (2013). Data collection from both years included number of hand consults and need for transfer. From the 2014 data, we also recorded the use of telemedicine, type of transfer, distance of transfer, and time to disposition. Results: During 2013 (pre-telemedicine), there were 263 hand traumas identified. In all, 191 (73%) injuries required transfer to a higher level of care, while 72 (23%) were managed locally. In the first year of the telemedicine program (2014), a total of 331 hand injuries were identified. A total of 298 (90%) resulted in telemedicine consultation with 65% (195) utilizing video encounters. After telemedicine consultation, local management was recommended for 164 injuries (55%) while transfer was recommended for 134 (45%). Using telemedicine, there was a significant decrease in the percentage of transfer for hand injuries (P < .001). Conclusions: The telemedicine program was well utilized and provided patients throughout the state with continuous access to fellowship trained hand surgeons including regions where hand subspecialty care is not available. The program resulted in a significant decrease in the number of hospital transfers for the management of acute hand trauma.     

Two preadipocyte subtypes cloned from human omental fat

To determine whether the characteristics of preadipocytes derived from human fat are uniform or variable, we developed methods for culturing and differentiating cloned human preadipocytes. Individual human omental preadipocytes were cultured for six weeks. The number of cells varied considerably among clones derived from the same subject, implying that human preadipocytes vary in replicative capacity. Indeed, two cell subtypes were found in human omental fat; one type replicated slowly and the other was capable of extensive replication. Cells of both subtypes were capable of differentiation into adipocytes, confirming that both subtypes were preadipocytes. When rat perirenal and epididymal preadipocytes were cloned, a slowly replicating and an extensively replicating preadipocyte subtype were also found. It is proposed that preadipocytes of the rapidly and the slowly replicating subtypes may be at different stages along the pathway between uncommitted precursor cells and differentiated adipocytes.     

重度肥胖患者胃肠分流术后低氧血症机制的分析

目的　研究重度肥胖对胃肠分流术后动脉血氧分压的影响。方法　对 6 1例进行胃肠分流术的重度肥胖患者及 5 5例择期腹部手术的正常体重患者进行术前肺功能、术前及术后 1～ 5d的血气分析检测。结果　肥胖组术后1～ 5d、对照组术后 1～ 2d的动脉血氧分压较术前显著下降 (P <0 .0 5 ) ;肥胖组术后 1～ 2d动脉血氧分压与其最大分钟通气量及腰臀比显著相关 (P <0 .0 0 0 1)。结论　重度肥胖者较正常体重患者在腹部手术后发生低氧血症的程度较严重且持续时间长。     

Proteinase activated receptor 2: Role of extracellular loop 2 for ligand-mediated activation

1. Rat proteinase-activated receptor-2 (PAR2) variants were stably expressed in rat KNRK cells: (a) wild-type (wt) - PAR2; (b) PAR2PRR, with the extracellular loop 2 (EL-2) sequence P231E232E233mutated to PRR and (c) PAR2NET, with the EL-2 sequence, PEEV changed to NETL. Cell lines were evaluated for their sensitivity (calcium signalling) towards trypsin and the receptor-activating peptides, SLIGRL-NH2, SLIGEL-NH2, trans-cinnamoyl(tc)-LIGRLO-NH2, and SFLLR-NH2. 2. SLIGEL-NH2 exhibited low potency (1 : 200 relative to SLIGRL-NH2) in wild-type PAR2. Its activity was increased 5 fold in PAR2PRR, but it was inactive in PAR2NET. 3. In PAR2PRR, the potencies of SLIGRL-NH2, tc-LIGRLO-NH2, and SFLLR-NH2 were decreased by 80 - 100 fold. But, the potency of trypsin was decreased by only 7 fold. 4. In PAR2NET, highly homologous in EL-2 with proteinase-activated receptor-1 (PAR1), the potency of the PAR1-derived peptide, SFLLR-NH2, was reduced by 100 fold compared with wt-PAR2, whereas the potency of the PAR2-derived AP, SLIGRL-NH2 was reduced 10 fold. In contrast, the potency of trypsin in PAR2NET was almost the same as in wt-PAR2. 5. We conclude that the acidic EL-2 tripeptide, PEE, in PAR2 plays an important role in governing agonist activity. 6. The data obtained with the PEEV-->NETL mutation suggested: (a) that SLIGRL-NH2 and SFLLR-NH2 interact in a distinct manner with PAR2 and (b) that SFLLR-NH2 may interact differently with PAR2 than it does with PAR1. 7 The differential reductions in the potencies of SLIGRL-NH2, compared with trypsin in the PAR2PRR and PAR2NET cell lines point to differences between the interactions of the trypsin-revealed tethered ligand and the free receptor-activating peptide with PAR2.     

Bacterial β-lactamase is efficiently secreted in Saccharomyces cerevisiae under control of the invertase signal sequence

Summary The enzyme -lactamase, a secretory protein that is located in the Escherichia coli periplasmic space, can be highly expressed in Saccharomyces cerevisiae. Although the protein can cross eukaryotic membranes, it is only inefficiently secreted by yeast. To determine whether the lack of secretion in yeast is due to the nature of the bacterial signal sequence, it was replaced with the signal peptide of yeast invertase. The presence of the invertase signal peptide led to -lactamase secretion of up to 75%. The results indicate that the bacterial signal peptide is not functional in yeast, although cleavage can take place at the authentic processing site. The mature enzyme does not interfere with the yeast secretion pathway.     

Associations between patient report of symptoms and anatomic impairment visible on lumbar magnetic resonance imaging

STUDY DESIGN: A cross-sectional study comparing the relationship of symptoms with anatomic impairment visible on lumbar magnetic resonance imaging in 408 symptomatic subjects. OBJECTIVE: To determine how various anatomic impairments, including the magnitude and location of nerve compression visible on lumbar magnetic resonance imaging, are associated with patient reports of pain, weakness, and dysesthesia. SUMMARY AND BACKGROUND DATA: Anatomic impairments of the intervertebral disc, radicular canal, and associated soft tissues are prevalent in people with and those without low back pain or lower extremity radiculopathy. This has led to confusion in differentiating between symptom generators and benign variation visible on lumbar magnetic resonance imaging. Recent literature has suggested that the presence of nerve compression is an important finding in the prediction of symptoms. However, the threshold for meaningful nerve compression has not been described. METHODS: In this study, 408 participants undergoing a diagnostic workup for low back pain, radiculopathy, and/ or completed a survey and pain drawing. Participants underwent standardized lumbar magnetic resonance imaging using a 1.5-T scanner. Two classification systems describing the spatial distribution of symptoms were developed. An additional system to quantify the magnitude of nerve and thecal sac compression was created. All systems were assessed for reliability, after which comparisons among variables were performed using Chi2 as well as simple and multiple logistic regression analysis. RESULTS: The reliability coefficients for categorizing patients on the basis of pain drawing ranged from 0. 75 to 0.88. The S1-S2 segmental distribution was the most commonly reported location of symptoms, followed by L4-L5. The most common magnetic resonance imaging diagnosis was "unremarkable," followed by "disc impairment without nerve compression." Disc extrusion was present in 10.8% of participants. The reliability of classifying nerve compression visible on magnetic resonance imaging ranged from 0.27 to 1. Nerve compression was present in 37% of participants, and 18% had severe nerve compression. There were no significant associations between segmental distribution of symptoms and the presence of anatomic impairment. However, according to a collapsed classification scale, severe nerve compression and disc extrusion were predictive of pain distal to the knee (odds ratios, 2.72 and 3. 34). The self-report of weakness was associated mildly with severe nerve compression and disc extrusion, but not with other findings. Magnetic resonance imaging findings did not predict self-reports of dysesthesia. CONCLUSIONS: The presence of disc extrusion and/or ipsilateral, severe nerve compression at one or multiple sites is strongly associated with distal leg pain. Mild to moderate nerve compression, disc degeneration or bulging, and central spinal stenosis are not significantly associated with specific pain patterns. Although segmental distributions of pain can be determined reliably from pain drawings, this finding alone is of little use in predicting lumbar impairment. The self-report of lower extremity weakness or dysesthesia is not significantly related to any specific lumbar impairments. [Key words: back pain, diagnosis, magnetic resonance imaging, nerve compression, pain drawing, pathology]