Costello syndrome: Clinical phenotype,genotype, and management guidelines

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence‐based guidelines due to the lack of data for this rare condition.     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

Mycoplasma hyopneumoniae increases intracellular calcium release in porcine ciliated tracheal cells

We investigated the effects of intact pathogenic Mycoplasma hyopneumoniae, nonpathogenic M. hyopneumoniae, and Mycoplasma flocculare on intracellular free Ca2+ concentrations ([Ca2+]i) in porcine ciliated tracheal epithelial cells. The ciliated epithelial cells had basal [Ca2+]i of 103 +/- 3 nM (n = 217 cells). The [Ca2+]i increased by 250 +/- 19 nM (n = 47 cells) from the basal level within 100 s of the addition of pathogenic M. hyopneumoniae strain 91-3 (300 microg/ml), and this increase lasted approximately 60 s. In contrast, nonpathogenic M. hyopneumoniae and M. flocculare at concentrations of 300 microg/ml failed to increase [Ca2+]i. In Ca2+-free medium, pathogenic M. hyopneumoniae still increased [Ca2+]i in tracheal cells. Pretreatment with thapsigargin (1 microM for 30 min), which depleted the Ca2+ store in the endoplasmic reticulum, abolished the effect of M. hyoneumoniae. Pretreatment with pertussis toxin (100 ng/ml for 3 h) or U-73122 (2 microM for 100 s), an inhibitor of phospholipase C, also abolished the effect of M. hyopneumoniae. The administration of mastoparan 7, an activator of pertussis toxin-sensitive proteins G(i) and G(o), increased [Ca2+]i in ciliated tracheal cells. These results suggest that pathogenic M. hyopneumoniae activates receptors that are coupled to G(i) or G(o), which in turn activates a phospholipase C pathway, thereby releasing Ca2+ from the endoplasmic reticulum. Thus, an increase in Ca2+ may serve as a signal for the pathogenesis of M. hyopneumoniae.     

Increased production of proinflammatory cytokines following infection with porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae

Induction of the proinflammatory cytokines interleukin-1 (IL-1) (alpha and beta), IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor alpha (TNF-alpha) in pulmonary alveolar macrophages (PAMs) was assessed following experimental infection with porcine reproductive and respiratory syndrome virus (PRRSV) and/or Mycoplasma hyopneumoniae by using in vivo and in vitro models. The in vivo model consisted of pigs infected with PRRSV and/or M. hyopneumoniae and necropsied at 10, 28, or 42 days postinfection. Pigs infected with both pathogens had a greater percentage of macroscopic lung lesions, increased clinical disease, and slower viral clearance than pigs infected with either pathogen alone. The pigs infected with both PRRSV and M. hyopneumoniae had significantly increased levels of mRNA for many proinflammatory cytokines in PAMs collected by bronchoalveolar lavage (BAL) at all necropsy dates compared to those in uninfected control pigs. Increased levels of IL-1beta, IL-8, IL-10, and TNF-alpha proteins in BAL fluid, as measured by enzyme-linked immunosorbent assay, confirmed the increased cytokine induction induced by the pathogens. An in vitro model consisted of M. hyopneumoniae-inoculated tracheal ring explants cultured with PRRSV-infected PAMs. PAMs were harvested at 6 or 15 h postinfection with either or both pathogens. The in vitro study detected increased IL-10 and IL-12 mRNA levels in PAMs infected with PRRSV at all time periods. In addition, IL-10 protein levels were significantly elevated in the culture supernatants in the presence of M. hyopneumoniae-inoculated tracheal ring explants. The increased production of proinflammatory cytokines in vivo and in vitro associated with concurrent M. hyopneumoniae and PRRSV infection may play a role in the increased rates of pneumonia associated with PRRSV infection. The increased levels of IL-10 may be a possible mechanism that PRRSV and M. hyopneumoniae use to exacerbate the severity and duration of pneumonia induced by PRRSV and modulate the respiratory immune response.     

Malignant hyperthermia 2020

Malignant hyperthermia is defined in the International Classification of Diseases as a progressive life-threatening hyperthermic reaction occurring during general anaesthesia. Malignant hyperthermia has an underlying genetic basis, and genetically susceptible individuals are at risk of developing malignant hyperthermia if they are exposed to any of the potent inhalational anaesthetics or suxamethonium. It can also be described as a malignant hypermetabolic syndrome. There are no specific clinical features of malignant hyperthermia and the condition may prove fatal unless it is recognised in its early stages and treatment is promptly and aggressively implemented. The Association of Anaesthetists has previously produced crisis management guidelines intended to be displayed in all anaesthetic rooms as an aide memoire should a malignant hyperthermia reaction occur. The last iteration was produced in 2011 and since then there have been some developments requiring an update. In these guidelines we will provide background information that has been used in updating the crisis management recommendations but will also provide more detailed guidance on the clinical diagnosis of malignant hyperthermia. The scope of these guidelines is extended to include practical guidance for anaesthetists dealing with a case of suspected malignant hyperthermia once the acute reaction has been reversed. This includes information on care and monitoring during and after the event; appropriate equipment and resuscitative measures within the operating theatre and ICU; the importance of communication and teamwork; guidance on counselling of the patient and their family; and how to make a referral of the patient for confirmation of the diagnosis. We also review which patients presenting for surgery may be at increased risk of developing malignant hyperthermia under anaesthesia and what precautions should be taken during the peri-operative management of the patients.     

Wound cleansing by irrigation for implant surgery

Wound irrigation is an adjunct to all implant surgeries involving surgical incisions or arthroplasties. An understanding of the physics of wound irrigation provides a scientific basis for recommending wound irrigation systems for implant surgery. When inserting implants through surgical incisions, a low-pressure irrigation system is recommended for removing blood from the wound surface. In contrast, high-pressure irrigation systems are indicated to cleanse the intramedullary canal before cemented arthroplasty. With the advent of static and dynamic pressure transducers, irrigation systems can now be specifically designed to achieve these goals.     

Improved quality of re-sliced MR images using re-normalized sinc interpolation.

This article shows that re-normalizing the interpolation kernel for a constant integral can make a significant improvement in performance of sinc interpolation methods. A comparison was performed between standard and re-normalized sinc kernels of various sizes using data from four commonly used magnetic resonance (MR) imaging sequences. Standard rotations were performed and compared with a "gold standard" data set generated by use of a large (13 x 13 x 13) sinc kernel. Measurements of systematic pixel intensity offset error and variance of generated residuals were used to estimate resultant interpolation error. Theoretical estimates of the consequent savings in computation time were compared with the measured time required for each algorithm and with the automated image registration (AIR) program. The use of a small (5 x 5 x 5) re-normalized kernel produced relative errors comparable to those in the gold standard data set, allowing saving in computation time of up to 30 times in comparison with standard sinc interpolation. This approach brings the implementation of MR volume re-slicing much closer to the demands of a clinical environment. J. Magn. Reson. Imaging 1999;10:582-588.     

Rectus muscle orbital wall fixation: a reversible profound weakening procedure.

INTRODUCTION: Surgical treatment of third nerve palsy, sensory exotropia and strabismus secondary to anomalous innervation of the rectus muscles, frequently require large rectus muscle recessions in an attempt to maintain alignment in the primary position and reduce the effects of misinnervation. The aim of this study was to describe and evaluate the results of inactivation of a rectus muscle by its attachment to the adjacent orbital wall. METHODS: Seven subjects diagnosed with third-nerve palsy (three cases), Duane syndrome (two cases), sensory exotropia (one case), and congenital aberrant innervation of vertical rectus muscles (one case) underwent rectus muscle inactivation by orbital wall fixation. The rectus muscle was disinserted from the globe and reattached to the adjacent orbital periosteum using non-absorbable sutures. This surgery was performed on the lateral rectus muscle in six subjects, and surgery was performed on both ipsilateral vertical rectus muscles in one. RESULTS: Postoperatively four of six patients were aligned within 12 prism diopters of orthotropia in primary position. All patients had improvement of the anomalous head posture. In Duane syndrome, lateral rectus inactivation markedly reduced co-contraction and globe retraction. No overcorrections resulted. CONCLUSION: A rectus muscle may be functionally inactivated when its insertion is attached to the orbital periosteum. Advantages of this procedure over extirpation and free tenotomy include permanent disinsertion of the muscle from globe and reversibility.     

分娩期连续电子胎心监护用于胎儿评估

1背景 在美国，每4例孕妇中有3例在产群中及分娩时使用电子胎儿监护（EFM）（NCHS1993）。1989年，美国妇产科学院（ACOG1989）发表了一项声明，对于低危妊娠既可使用EFM，也可使用间断性胎心听诊；但是，美国预防保健委员会（USPSTF1989）和加拿大的定期健康检查委员会（CTFPHE1994）对高危妊娠仍保留使用EFM。尽管有人对EFM的效果和安全性表示担忧（Thacker 1987：Thacker 1995），