Meningococcal septicaemia complications involving skin and underlying deeper tissues - management considerations and outcome

Objective: To describe surgical experience with purpura fulminans related to meningococcaemia in a single institution, and to suggest a management protocol. Methods: A retrospective review was done of patients admitted to the intensive care unit at Red Cross War Memorial Children's Hospital in Cape Town with the clinical diagnosis of purpura fulminans. Results: During a 28-year period (1977 - 2005) 112 children (average age 3.4 years) were treated for meningococcaemia with purpura fulminans. Overall mortality was 10.7%. Local treatment consisted of measures to improve circulation, infection control and healing of necrotic tissue. Demarcation of necrotic areas was evident at 5.5 days and the average area of skin necrosis was 14% total body surface area (range 2 - 85%). The lower limbs were predominantly affected. Purpura fulminans resolved in 35 children (31.2%) without skin necrosis. Skin grafting was required in 77 children (68.8%). Factors associated with a poor outcome for peripheral extremity salvage were progressive irreversible skin changes, early disappearance of distal pulses, tense cold swollen extremities and intense pain on passive movement of the affected extremity. Amputations were performed proximal to the area of necrosis, on average 27 days after injury. Conclusions: Meningococcaemia is a disease with potentially devastating consequences. Early surgical consultation is essential. Skin- and soft-tissue-releasing incisions should be considered early to reduce the incidence of extremity necrosis. Small necrotic areas usually separate spontaneously with secondary healing or can be excised and sutured. Larger necrotic areas should be excised only after demarcation has been established, and can be covered with delayed skin grafting. Amputation should be conservative but may require revision

Ultra-low threshold CW Triply Resonant OPO in the near infrared using Periodically Poled Lithium Niobate

We have operated a CW triply resonant OPO using a PPLN crystal pumped by a Nd:YAG laser at 1.06 micron and generating signal and idler modes in the 2-2.3 micron range. The OPO was operated stably in single mode operation over large periods of time with a pump threshold as low as 500 microwatts.Comment: 7 pages, 5 figures, submitted to JEOS

Revisiting the anatomy of the ilio-inguinal/iliohypogastric nerve block

BACKGROUND : The ilio-inguinal/iliohypogastric nerve block (INB) is one of the most common peripheral nerve block techniques in pediatric anesthesia, which is largely due to the introduction of ultrasound (US) guidance. Despite the benefits of US guidance, the absence of an US machine should not deter the provider from performing INB, considering that many institutions, especially in developing countries, cannot afford to provide ultrasound machines in their anesthesiology departments. The aim of this study was to revisit the anatomical position of the ilio-inguinal and iliohypogastric nerves in relation to the anterior superior iliac spine (ASIS), in a large sample of neonatal cadavers, and compare the results with a similar group in a previously published US-guided study. METHODS : With Ethics Committee approval, the ilio-inguinal and iliohypogastric nerves were carefully dissected in 54 neonatal cadavers. RESULTS : In the total sample, the ilio-inguinal nerve was found to be 2.2 1.2 mm from the ASIS, on a line connecting the ASIS to the umbilicus. The iliohypogastric nerve was on average 3.8 1.3 mm from the ASIS. For the entire sample, the optimal needle insertion site was 3.00 mm from the ASIS. Although there is a strong correlation between the needle insertion point and the weight of the neonate, this will only ‘fit’ for 60%of the population. CONCLUSION : The linear regression formula; needle insertion distance (mm) = 0.6 9 weight + 1.8 can be used as a guideline for the position of the ilio-inguinal and iliohypogastric nerves.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1460-9592hb201

A 750 mW, continuous-wave, solid-state laser source at 313 nm for cooling and manipulating trapped 9Be+ ions

We present a solid-state laser system that generates 750 mW of continuous-wave single-frequency output at 313 nm. Sum-frequency generation with fiber lasers at 1550 nm and 1051 nm produces up to 2 W at 626 nm. This visible light is then converted to UV by cavity-enhanced second-harmonic generation. The laser output can be tuned over a 495 GHz range, which includes the 9Be+ laser cooling and repumping transitions. This is the first report of a narrow-linewidth laser system with sufficient power to perform fault-tolerant quantum-gate operations with trapped 9Be+ ions by use of stimulated Raman transitions.Comment: 9 pages, 4 figure

Bilateral infraorbital nerve blocks decrease postoperative pain but do not reduce time to discharge following outpatient nasal surgery

While infraorbital nerve blocks have demonstrated analgesic benefits for pediatric nasal and facial plastic surgery, no studies to date have explored the effect of this regional anesthetic technique on adult postoperative recovery. We designed this study to test the hypothesis that infraorbital nerve blocks combined with a standardized general anesthetic decrease the duration of recovery following outpatient nasal surgery. At a tertiary care university hospital, healthy adult subjects scheduled for outpatient nasal surgery were randomly assigned to receive bilateral infraorbital injections with either 0.5% bupivacaine (Group IOB) or normal saline (Group NS) using an intraoral technique immediately following induction of general anesthesia. All subjects underwent a standardized general anesthetic regimen and were transported to the recovery room following tracheal extubation. The primary outcome was the duration of recovery (minutes) from recovery room admission until actual discharge to home. Secondary outcomes included average and worst pain scores, nausea and vomiting, and supplemental opioid requirements. Forty patients were enrolled. A statistically significant difference in mean [SD] recovery room duration was not observed between Groups IOB and NS (131 [61] min vs 133 [58] min, respectively; P = 0.77). Subjects in Group IOB did experience a reduction in average pain on a 0–100 mm scale (mean [95% confidence interval]) compared to Group NS (−11 [−21 to 0], P = 0.047), but no other comparison of secondary outcomes was statistically significant. When added to a standardized general anesthetic, bilateral IOB do not decrease actual time to discharge following outpatient nasal surgery despite a beneficial effect on postoperative pain

SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells

Targeting anti-apoptotic proteins can sensitize tumor cells to conventional chemotherapies or other targeted agents. Antagonizing the Inhibitor of Apoptosis Proteins (IAPs) with mimetics of the pro-apoptotic protein SMAC is one such approach. We used sensitization compound screening to uncover possible agents with the potential to further sensitize lung adenocarcinoma cells to the SMAC mimetic Debio 1143. Several compounds in combination with Debio 1143, including taxanes, topoisomerase inhibitors, and bromodomain inhibitors, super-additively inhibited growth and clonogenicity of lung adenocarcinoma cells. Co-treatment with Debio 1143 and the bromodomain inhibitor JQ1 suppresses the expression of c-IAP1, c-IAP2, and XIAP. Non-canonical NF-κB signaling is also activated following Debio 1143 treatment, and Debio 1143 induces the formation of the ripoptosome in Debio 1143-sensitive cell lines. Sensitivity to Debio 1143 and JQ1 co-treatment was associated with baseline caspase-8 expression. In vivo treatment of lung adenocarcinoma xenografts with Debio 1143 in combination with JQ1 or docetaxel reduced tumor volume more than either single agent alone. As Debio 1143-containing combinations effectively inhibited both in vitro and in vivo growth of lung adenocarcinoma cells, these data provide a rationale for Debio 1143 combinations currently being evaluated in ongoing clinical trials and suggest potential utility of other combinations identified here

YY1 Regulates Melanocyte Development and Function by Cooperating with MITF

Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP–seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1) gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF)—a general mechanism which may confer tissue-specific gene expression in multiple lineages

Intestinal fatty-acid binding protein and gut permeability responses to exercise

Purpose Intestinal cell damage due to physiological stressors (e.g. heat, oxidative, hypoperfusion/ischaemic) may contribute to increased intestinal permeability. The aim of this study was to assess changes in plasma intestinal fatty acid-binding protein (I-FABP) in response to exercise (with bovine colostrum supplementation, Col, positive control) and compare this to intestinal barrier integrity/permeability (5 h urinary lactulose/rhamnose ratio, L/R). Methods In a double-blind, placebo-controlled, crossover design, 18 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac). For each arm participants performed two baseline (resting) intestinal permeability assessments (L/R) pre-supplementation and one post-exercise following supplementation. Blood samples were collected pre- and post-exercise to determine I-FABP concentration. Results Two-way repeated measures ANOVA revealed an arm?×?time interaction for L/R and I-FABP (P?<?0.001). Post hoc analyses showed urinary L/R increased post-exercise in Plac (273% of pre, P?<?0.001) and Col (148% of pre, P?<?0.001) with post-exercise values significantly lower with Col (P?<?0.001). Plasma I-FABP increased post-exercise in Plac (191% of pre-exercise, P?=?0.002) but not in the Col arm (107%, P?=?0.862) with post-exercise values significantly lower with Col (P?=?0.013). Correlations between the increase in I-FABP and L/R were evident for visit one (P?=?0.044) but not visit two (P?=?0.200) although overall plots/patterns do appear similar for each. Conclusion These findings suggest that exercise-induced intestinal cellular damage/injury is partly implicated in changes in permeability but other factors must also contribute

The effect of bovine colostrum supplementation on intestinal injury and circulating intestinal bacterial DNA following exercise in the heat

Purpose Exercise-induced changes in intestinal permeability are exacerbated in the heat. The aim of this study was to determine the effect of 14 days of bovine colostrum (Col) supplementation on intestinal cell damage (plasma intestinal fatty acid-binding protein, I-FABP) and bacterial translocation (plasma bacterial DNA) following exercise in the heat. Methods In a double-blind, placebo-controlled, crossover design, 12 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac) consisting of 60 min treadmill running at 70% maximal aerobic capacity (30 ??C, 60% relative humidity). Blood samples were collected pre-exercise (Pre-Ex), post-exercise (Post-Ex) and 1 h post-exercise (1 h Post-Ex) to determine plasma I-FABP concentration, and bacterial DNA (for an abundant gut species, Bacteroides). Results Two-way repeated measures ANOVA revealed an arm ?~ time interaction for I-FABP (P = 0.005, with greater Post- Ex increase in Plac than Col, P = 0.01: Plac 407 ?} 194% of Pre-Ex vs Col, 311 ?} 134%) and 1 h Post-Ex (P = 0.036: Plac 265 ?} 80% of Pre-Ex vs Col, 229 ?} 56%). There was no interaction (P = 0.904) but there was a main effect of arm (P = 0.046) for plasma Bacteroides/total bacterial DNA, with lower overall levels evident in Col. Conclusion This is the first investigation to demonstrate that Col can be effective at reducing intestinal injury following exercise in the heat, but exercise responses (temporal pattern) of bacterial DNA were not influenced by Col (although overall levels may be lower).publishersversionPeer reviewe