Cerebral Palsy

Human embryonic and induced pluripotent stem cells (ESCs, iPSCs) that are cultured for an extended period of time are susceptible to genomic instability. Chromosomal aberrations decrease the reliability and reproducibility of experiments and could deem the cells unusable for therapeutic purposes. The genetic stability of human ESCs and iPSCs is commonly monitored by karyotype analysis. However, this low-resolution technique can only identify large aneuploidies. A reliable, high-resolution technique to detect genomic aberrations at a cost comparable to karyotyping is needed to better characterize stem cell lines. We have designed a stem cell focused array-comparative genomic hybridization microarray that covers the entire genome at high resolution with increased probe coverage in over 60 stem cell associated genes and more than 195 cancer related genes. Several iPSC lines were analyzed using the focused microarray and compared with either karyotyping or a standard Agilent 44K microarray. In addition to the abnormalities detected by these platforms, the custom microarray identified several small duplications spanning stem cell and/or cancer related genes. Scientists using a stem cell focused microarray to characterize their stem cells will be aware of the structural variants present in their cells and be more confident in their experimental results.

BACKGROUND: In patients with previous myocardial infarction (MI), assessment of myocardial viability and physiological significance of coronary artery stenoses are essential for appropriate guidance of revascularization. The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and myocardial viability as assessed by gated SPECT MIBI perfusion scintigraphy in patients with previous MI undergoing elective PCI. METHODS: The study population consisted of 26 patients (mean age 55 +/- 7 years; 21 male) with a previous MI and a significant coronary stenosis in a single infarct-related coronary vessel for which PCI was being performed. In all patients, FFR was evaluated before and immediately after PCI. SPECT imaging was done before and 3 +/- 1 months after PCI. A region representing the MI was considered viable if MIBI uptake was >/=55% of the normal region. Improvement in perfusion after revascularization was considered achieved if perfusion abnormalities decreased by 5% or more and there was a decrease in segmental score of >/=1 in three segments in PCI-related vascular territory. RESULTS: Extent of perfusion abnormalities decreased from 32 +/- 16% to 27 +/- 19% after PCI (P < .001). In patients with myocardial viability in comparison to patients with no viability, there was significant difference in FFR before PCI (.57 +/- .14 vs .76 +/- .12, P = .002), despite almost the same values of diameter stenosis of infarct-related artery (63 +/- 8% vs 64 +/- 3%, respectively, P = .572). In addition, FFR prior to PCI was related to improvement in perfusion abnormalities after revascularization (P = .047), as well as with peak activity of creatine-kinase measured during previous MI (r = .56, P = .005). CONCLUSION: Lower values of FFR before angioplasty are associated with myocardial viability and functional improvement as assessed by SPECT perfusion scintigraphy.

A second questionnaire survey of Japanese patients with thrombotic microangiopathy (TMA) was carried out to investigate the frequency, laboratory abnormalities and outcome in 2004 and 2005. The first and second surveys evaluated 397 patients including 19 with familial TMA and 378 with acquired TMA. The patients with acquired TMA included 165 with Escherichia coli O-157 infection-related TMA (O-157 TMA), 70 with ADAMTS13-related TMA (ADAMTS13 TMA) and 38 with other types of TMA (other TMA). The rate of ADAMTS13 TMA was significantly higher in patients with collagen diseases than in patients with all other underlying diseases (p < 0.001). The treatment of acquired TMA included plasma exchange (PE), steroids, antiplatelet agents, and anticoagulants, PE was carried out in 91.4% of patients with ADAMTS13 TMA, 68.4% of patients with other TMA and 12.7% of patients with O-157 TMA. The efficacy of PE and steroid therapy tended to be higher in patients with ADAMTS13 TMA than in those with other TMA. The complete remission rate was the highest and the mortality rate was the lowest in the patients with O-157 TMA. The mortality rate tended to be lower in patients with ADAMTS13 TMA than in those with other TMA. However, not all of the patients in our study were examined for ADAMTS13 at the time that this questionnaire survey was conducted.

The objective of this study was to document persistent pulmonary symptoms and pulmonary function abnormalities in adults surviving hantavirus pulmonary syndrome (HPS). Acute infection by most hantaviruses result in mortality rates of 25-35%, while in Panama the mortality rate of 10% is contrasted by an unusually high incidence. In all types of HPS, the viral prodrome, cardiopulmonary phase due to massive pulmonary capillary leak syndrome, and spontaneous diuresis are followed by a convalescent phase with exertional dyspnea for 3-4 weeks, but the frequency of persistent symptoms is not known. In this observational study of a convenience sample, 14 survivors of HPS caused by Choclo virus infection in Panama and 9 survivors of HPS caused by Sin Nombre virus infection in New Mexico completed a questionnaire and pulmonary function tests up to 8 years after infection. In both groups, exertional dyspnea persisted for 1-2 years after acute infection in 43% (Panama) and 77% (New Mexico) of survivors surveyed. Reduction in midexpiratory flows (FEF(25-75%)), increased residual volume (RV), and reduced diffusion capacity (D(L)CO/VA) also were common in both populations; but the severity of reduced expiratory flow did not correlate with exertional dyspnea. Symptoms referable to previous hantavirus infection had resolved within 3 years of acute infection in most but not all patients in the Panama group. Temporary exertional dyspnea and reduced expiratory flow are common in early convalescence after HPS but resolves in almost all patients.

An eccrine nevus is a rare hamartoma characterized by an increase in the number or size of eccrine glands. Eccrine nevi usually present as localized hyperhidrosis and are not associated with overlying skin abnormalities. However, among the cases that have been reported in the literature, some unique presentations of eccrine nevi have been demonstrated, including a pigmented patch, a depressed nodule, linear papules, and a sacral skin tag. Herein, we report two unusual cases of coccygeal polypoid eccrine nevi and review the literature.

Branchio-oculo-facial syndrome (BOFS) is a rare, autosomal dominant disorder. It is characterized by distinct craniofacial abnormalities including abnormal location of the ears, aplastic cervical skin lesions, malformed auricles, conductive hearing loss, ocular abnormalities, and cleft lip and palate. Herein, we describe a case of BOFS with persistent aplasia cutis of the neck in a 5-year-old girl.

PurposeThe purpose of this study was to present an association between diabetic macular oedema (DME) and vitreoretinal interface abnormalities using 3D spectral domain optical coherence tomography (SD-OCT).MethodsIn a retrospective study, charts and SD-OCT of consecutive patients with diffuse or focal DME were reviewed. Only one randomly chosen eye per patient with DME was included, and eyes that had another retinopathy that could affect the study analysis or that underwent vitreoretinal surgery were excluded.ResultsOut of 58 eyes (58 patients) with DME, 11 eyes (19.0%) had vitreofoveal traction (Group A), either unifocally (n=6) or multifocally; that is, associated with additional extrafoveal traction site(s). Group B comprised 20 eyes (34.5%) that had sole extrafoveal vitreous traction, at either retinal and/or papillary sites. In each, the retinal oedema underlying extrafoveal traction was in continuum in at least one site with that at the central macula, as verified by the macular maps, thus presented as diffuse macular oedema. In Group C, 13 eyes (22.4%) had an epiretinal membrane (ERM), 1.5 x 3 mm to >/=6 x 6 mm in size that overlaid diffuse oedematous macula. Group D included 14 eyes (24.1%) that had neither vitreous traction nor ERM; 12 (20.7%) of them had DME secondary to leaking microaneurysms with or without leaking capillary beds, and the remaining two had leakage from non-microaneurysms sources.ConclusionsDME was detected by the SD-OCT to be associated with sole extrafoveal vitreous traction in one-third of the patients. Further studies are required to evaluate the clinical consequences of these observations.Eye advance online publication, 4 June 2010; doi:10.1038/eye.2010.80.

Recent publications assessing colonoscopy missed rates of colorectal cancer have generated efforts toward colonoscopy quality improvement. To date, esophagogastroduodenoscopy (EGD) has escaped similar scrutiny in Western populations. Raftopoulos et al. (1) report an upper gastrointestinal cancer missed rate of up to 6.7% in a cohort of 28,000 patients who underwent EGD at a hospital-based endoscopy unit in Perth, Western Australia. Of the missed esophageal and gastric cancers, approximately 80% of patients had alarm symptoms and 73% had abnormalities reported at the time of EGD. The missed cancers may not have been visualized, or were visualized and either not biopsied or biopsied inadequately, or interpreted incorrectly by pathologists. There was no difference in survival between the missed cancers and those detected at the index EGD.

Acute kidney injury (AKI) is an important clinical syndrome characterized by abnormalities in the hydroelectrolytic balance. Due to the high rates of morbidity and mortality (from 15% to 60%) associated with AKI, the study of its pathophysiology is critical in searching for clinical targets and therapeutic strategies. Severe sepsis is the major cause of AKI. The host response to sepsis involves an inflammatory response whereby the pathogen is initially sensed by innate immune receptors (PPR). When it persists, this immune response leads to secretion of pro-inflammatory products that induce organ dysfunction such as renal failure and consequently increased mortality. Moreover, the injured tissue releases molecules resulting from extracellular matrix degradation or dying cells that function as “alarmines”, which are recognized by PPR in the absence of pathogens in a second wave of injury. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) are the best characterized PRRs. They are expressed in many cell types and throughout the nephron. Their activation leads to translocation of nuclear factors and synthesis of pro-inflammatory cytokines and chemokines. The TLRs can interact with NLRs to form the multiprotein complex known as the inflammasome, leading to secretion of mature IL-1beta and IL-18. Experimental data shows that innate immune receptors, the inflammasome components, and pro-inflammatory cytokines play crucial roles not only in sepsis, but also in organ-induced dysfunction, especially in the kidneys. In this review, we discuss the significance of the innate immune receptors in the development of acute renal injury secondary to sepsis.

In addition to evidence supporting serotonergic modulation of respiratory rhythmogenesis, serotonergic mechanisms play a role in central respiratory chemoreception. We examined the role of serotonin 5HT1A receptors in respiratory rhythmicity and central respiratory chemosensitivity in in vitro brainstem preparations of the bullfrog tadpole, Rana catesbeiana. Spontaneous respiratory motor output was recorded from cranial nerve 7 at control bath pH (7.8) and hypercapnic bath pH (7.4) as bath concentrations of a 5HT1A receptor agonist were steadily increased from 0.5 to 25 microM. Activation of the 5HT1A receptor significantly altered the respiratory burst cycle. Significant increases in both gill and lung burst cycle were observed in response to bath application of 8-OH-DPAT; gill burst cycle in response to 8-OH-DPAT was influenced by bath pH, as gill burst cycle at bath pH 7.8 was not significantly increased at 0.5 or 5.0 microM 8-OH-DPAT. However, when the pH was reduced to 7.4 gill burst cycle was significantly increased at these same bath concentrations of 8-OH-DPAT. Gill burst amplitude was not altered in response to bath application of 8-OH-DPAT; however, lung burst amplitude was significantly decreased at 25.0 microM 8-OH-DPAT at bath pH 7.8. These data indicate that 5HT1A receptors are involved in neural respiratory rhythmogenic and chemoreceptive circuits in the bullfrog tadpole, and support the hypothesis that abnormalities in serotonergic systems may be an underlying component of Sudden Infant Death Syndrome.