Sharp Versus Blunt Needle: A Comparative Study of Penetration of Internal Structures and Bleeding in Dogs

Background and Objectives: Complications associated with interventional pain procedures have raised questions regarding the relative safety of sharp vs. blunt needles. It has been speculated that the incidence of hemorrhage, intraneural and/or intravascular injections may be reduced by the use of blunt needles. In this study we compared penetration and bleeding associated with sharp vs. blunt needle punctures. Methods: Attempts were made to insert blunt and sharp needles (18‐, 20‐, 22‐, and 25‐gauge) directly or percutaneously into kidney, liver, renal artery, intestine or spinal nerve/nerve root of anesthetized dogs. Penetration and bleeding were ascertained by direct vision through a surgical wound. Results: All attempts to directly puncture the kidney and liver with sharp needles were successful. All but one attempt to puncture a spinal nerve/nerve root with 20‐, 22‐, and 25‐gauge sharp needles were successful but half or less attempts to puncture the intestines were successful. All attempts to puncture the renal artery with sharp needles were successful. Blunt needles never punctured the renal artery, spinal nerve/nerve root and intestines and rarely penetrated the kidney (22‐ and 25‐gauge one time each). All attempts to puncture the liver with blunt needles were successful. Bleeding scores for kidney punctures were generally higher for larger sharp needles than for smaller ones. Bleeding scores for blunt needle punctures of the liver were generally smaller than for sharp needle puncture. Conclusion: Blunt needles are less likely than sharp ones to enter vital structures and/or produce hemorrhage. Thus, blunt needles may be preferable to sharp ones for performing interventional pain procedures.     

Reduction of physiological fluctuations in fMRI using digital filters

Data obtained from functional magnetic resonance imaging are often limtted by a low signal-to-noise ratio. The time-course data obtained from activated regions contain both system noise and physiological noise, primarily linked to the heart and respiratory rates, that are superimposed on task induced signals. Time averaging of a practical number of data sets is not very effective in improving the signal-to-noise ratio because netther system nor physiological noise is truly random. In this paper, a method is presented for fittering un-wanted physiological fluctuations, including aliased signals that are formed as a result of long repetition time (TR) values. A pulse oximeter was used to obtain cardiac and respiratory Information during the scanning period. Fintte impulse response band-reject digital fitters were designed to remove the physiological fluctuations. For comparison, cross-correlation analyses were performed at the same tevel of statistical significance on both fittered and unfiltered data. We demonstrate that this method can improve the detection of weak signals without increasing the probability of false positives.     

Efficient gene transfer to human epidermal keratinocytes on fibronectin: in vitro evidence for transduction of epidermal stem cells.

The epidermis is an attractive target for gene therapy because it is easily accessible and has great potential as an ectopic site for protein delivery in vivo. Genetically modified keratinocytes can be expanded in culture and used to generate three-dimensional skin equivalents, which can deliver therapeutic proteins either locally or systemically for the treatment of wounds or systemic diseases. Here we present an optimum protocol that yields consistently high retroviral gene transfer on a substrate of recombinant fibronectin (rFN). Gene transfer on rFN depends strongly on virus concentration and the density of target cells. Interestingly, the kinetics of gene transfer varies depending upon the origin--mouse or human--of virus-producer cells. Most notably, long-term growth and clonogenic assays show that transduction on rFN promotes gene transfer to epidermal stem cells and prevents loss of clonogenic potential due to exposure of cells to retroviral supernatant. In contrast, the traditional protocol transduces mostly differentiated keratinocytes. We also show that skin equivalents prepared from genetically modified keratinocytes display high levels of transgene expression, mainly in the suprabasal layers. Our results are important for cutaneous gene therapy and for biological studies that require efficient and permanent genetic modification.     

A Personalized Diagnostic and Treatment Approach for Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Adults

Objective

We assessed the clinical features and outcomes based on therapeutic options adopted during hospital stay for adult patients with macrophage activation syndrome and secondary hemophagocytic lymphohistiocytosis (MAS/sHLH).

Methods

We conducted a retrospective chart review of all adult patients (age ≥ 18 years) diagnosed with MAS/sHLH at our center between 2010 and 2015. Inclusion criteria for patients were diagnosis of MAS/sHLH during admission and patients meeting at least 5 out of 8 of Henter’s criteria or at least 4 out of 6 of the criteria that were tested.

Results

Nineteen adult patients with MAS/sHLH met the inclusion criteria from January 2010 to October 2015 (median age 48 years; female 68.4%). Treatment had been personalized, depending on the clinical presentation and course of disease. Majority of the patients received anakinra, cyclosporine, intravenous immunoglobulins (IVIG), and steroids. Fourteen (74%) patients survived, with clinical improvement by the time of discharge. After excluding the three patients with underlying leukemia/lymphoma who opted for palliative care and subsequently died, the survival rate was 88%.

Conclusion

A modified diagnostic and treatment protocol for adult patients with MAS/sHLH that incorporated graded introduction of medications based on clinical presentation and cytokine profile resulted in the best adult survival rate reported in literature.

     

Histone modifications predispose genome regions to breakage and translocation

Chromosome translocations are well-established hallmarks of cancer cells and often occur at nonrandom sites in the genome. The molecular features that define recurrent chromosome breakpoints are largely unknown. Using a combination of bioinformatics, biochemical analysis, and cell-based assays, we identify here specific histone modifications as facilitators of chromosome breakage and translocations. We show enrichment of several histone modifications over clinically relevant translocation-prone genome regions. Experimental modulation of histone marks sensitizes genome regions to breakage by endonuclease challenge or irradiation and promotes formation of chromosome translocations of endogenous gene loci. Our results demonstrate that histone modifications predispose genome regions to chromosome breakage and translocations.     

Complex papillary hyperplasia of the endometrium: An uncommon case report with cytopathological features and diagnostic implications

Papillary proliferations of the endometrium, without atypia have been uncommonly documented, including on cytology specimens. Herein, we present an uncommon case of a 55‐year‐old obese lady, on antihypertensive medications, who presented with history of irregular perimenopausal bleeding. A year ago, she was diagnosed with simple cystic hyperplasia on dilation and curettage specimen. Presently, she underwent endometrial aspiration. Cytology smears were prepared from the collected tissue specimen that was further submitted for histopathological analysis. Although the smears were initially diagnosed as negative for malignancy, the tissue sections were reported as a uterine papillary serous carcinoma (UPSC). Review of the smears revealed prominent overlapping clusters and papillary arrangements of relatively banal endometrial cells exhibiting focal metaplasia. Histopathology sections confirmed diagnosis of complex papillary hyperplasia (CPH). Immunohistochemical (IHC) stains reinforced this impression with diffuse estrogen receptor positivity, low Ki‐67/MIB1, and lack of diffuse p53 immunostaining. Subsequent hysterectomy, at the time of intraoperative consultation showed a small residual focus of CPH, restricted to endometrium with intramural leiomyomas and adenomyosis. This case is presented to highlight the fact that despite lack of significant atypia, cytological features like overlapping, clustering, and papillary formations are indicators of papillary lesions of the endometrium, including CPH, especially in postmenopausal women. On histopathology, in spite of conspicuous papillary formations, lack of significant nuclear pleomorphism, and tumor invasion are helpful features in avoiding an overdiagnosis of UPSC in such cases. IHC stains are supportive. Correct identification has significant therapeutic implications. Diagn. Cytopathol. 2015;43:163–168. © 2014 Wiley Periodicals, Inc.     

Understanding how combinatorial targeting of TLRs and TNFR family costimulatory members promote enhanced T cell responses

Introduction: Due to the ability of pathogen-associated molecular patters and tumor necrosis factor receptor (TNFR) family costimulatory agonists to boost T cell responses, studies have combined Toll-like receptor (TLR) ligands with TNFR family costimulatory receptor agonists to induce impressive and long-lasting T cell responses. Although some studies have determined how these combinatorial vaccines promote enhanced T cell responses, much remains unknown about the mechanism used by these combinations to promote synergistic T cell responses – especially in settings of infectious diseases or cancer.

Areas covered: In this review, we look in detail at the signaling pathways induced by combinatorial targeting of TLR and TNFR family costimulatory members that help them promote synergistic T cell responses. Understanding this can greatly aid the development of novel vaccine regimens that promote cellular immune responses, which is essential for treating certain infectious diseases and cancer.

Expert opinion: Vaccines against some infectious diseases as well as therapeutic cancer vaccines require cellular immunity. Therefore, we evaluate here how signaling pathways induced by TLR ligand and costimulatory agonist combinations promote enhanced T cell responses during immunization with model antigens, viral pathogens, or tumor antigens. Once pathways that drive these combinatorial vaccines to boost T cell activation are identified, they can be incorporated in vaccines designed to target pathogens or cancer.     

Artificial Control of Glottic Adduction for Aspiration by Orderly Recruitment in the Canine

Laryngeal adduction for swallowing chiefly involves contraction of the thyroarytenoid and lateral cricoarytenoid muscles to seal the glottic chink. Vocal cord elongation supplements closure through cricoarytenoid activation. Relaxation of the posterior cricoarytenoid muscle is also involved in the swallowing process. Recent interest has focused on stimulating the laryngeal nerves to protect the lower airway from conditions where normal muscular coordination may be disrupted (e.g., in aspiration following stroke). Unfortunately, electrical stimulation results in a generalized contraction of all the dependent intrinsic laryngeal muscles because the larger, more excitable axons fire before their smaller counterparts can be activated. In the physiological state, however, the smaller fibers are recruited first. The current study focuses on electronic manipulation of force in the glottic muscles involved in deglutition. We used a stimulator that could selectively activate the intrinsic laryngeal muscles based on their specific motor unit architectures. In 5 dogs, the circuit recruited the axons in the recurrent and superior laryngeal nerves from small to large. The muscles were identified according to the differential recruitment rates of their compound muscle action potentials as they appeared on the graph. The smaller axons in the thyroarytenoid recruited faster than the large ones found in the lateral cricoarytenoid muscles, with intermediate figures observed with the cricothyroid. The posterior cricoarytenoid presented with the slowest recruitment rates, as expected from this muscle's highest contingent of larger motor units. Latencies between the onsets of stimulations and muscle saturations also appeared stable. This approach to manipulating glottic force saves energy because it allows stimulating the adductory muscles with minimal interference from their abductor antagonist.     

Successful ablation of focal left atrial tachycardia using Stereotaxis NiobeTM remote magnetic navigation system

Stereotaxis Niobe^TM remote magnetic navigation system (MNS)(St Louise, USA), is a new technology that has applicationsin the field of catheter based ablation treatment of cardiacarrhythmias. Most if not all data on the feasibility, safety,and efficacy of the Stereotaxis Niobe^TM MNS comes from selectcentres where highly skilled personnel have acquired considerableexperience using this technology. Herein, we report a case wherethe Stereotaxis Niobe^TM MNS was successfully used to performremotely-controlled high density three-dimensional electroanatomicalmapping and radiofrequency ablation of a focal atrial tachycardiaoriginating from the anteroseptal region of the left atrium.     

Multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing Salmonella enterica (serotypes Typhi and Paratyphi A) from blood isolates in Nepal: surveillance of resistance and a search for newer alternatives.

OBJECTIVES: We evaluated the prevalence of multidrug resistance (MDR) and production of extended spectrum beta-lactamase (ESBL) by Salmonella enterica (serotypes Typhi and Paratyphi A) in a teaching hospital in Nepal. The MDR strains of S. enterica were also tested for susceptibility to newer antibiotics. METHODS: Blood cultures were obtained from 4105 patients with febrile illnesses. Isolates of S. enterica were serotyped and antibiotic susceptibility testing was carried out using disk diffusion (Kirby-Bauer) and E-tests. ESBL screening and phenotype confirmation were done following National Committee for Clinical Laboratory Standards (NCCLS) recommendations for Escherichia coli. RESULTS: A total of 541 isolates of S. enterica serotypes Typhi (47%) and Paratyphi A (53%) were grown. Twenty-eight isolates (5%) of S. enterica were resistant to two or more antibiotics (MDR isolates), with a greater prevalence among serotype Paratyphi A (7%). All ESBL producers (three isolates) were serotype Paratyphi A. Most of the MDR S. enterica showed reduced susceptibility to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, ofloxacin, and ciprofloxacin, and had good susceptibility to extended-spectrum cephalosporins and carbapenems. Among the fluoroquinolones, gatifloxacin demonstrated better in vitro activity compared to levofloxacin, ciprofloxacin, and ofloxacin. CONCLUSIONS: A greater prevalence of S. enterica serotype Paratyphi A with higher rates of multidrug resistance and ESBL production is concerning for natives as well as travelers in Nepal since the current typhoid vaccines do not provide protection against this serotype.