Peripheral corneal edema following excision of a corneal keloid

A 49-year-old man presented with the rare finding of corneal keloid after corneal penetrating injury. The keloid was totally excised by lamellar keratectomy and was disconnected from a stromal scar, probably the perforation site. Symptomatic peripheral corneal edema developed postoperatively, extending 180°. The keloid had an effect similar to an avascular pannus in chronic bullous keratopathy. As long as the keloid was under the epithelium, the patient remained asymptomatic.     

Genotype–phenotype correlations analysis of mutations in the phenylalanine hydroxylase (PAH) gene

The aims of our research were to define the genotype–phenotype correlations of mutations in the phenylalanine hydroxylase (PAH) gene that cause phenylketonuria (PKU) among the Israeli population. The mutation spectrum of the PAH gene in PKU patients in Israel is described, along with a discussion on genotype–phenotype correlations. By using polymerase chain reaction/denaturing high-performance liquid chromatography (PCR/dHPLC) and DNA sequencing, we screened all exons of the PAH gene in 180 unrelated patients with four different PKU phenotypes [classic PKU, moderate PKU, mild PKU, and mild hyperphenylalaninemia (MHP)]. In 63.2% of patient genotypes, the metabolic phenotype could be predicted, though evidence is also found for both phenotypic inconsistencies among subjects with more than one type of mutation in the PAH gene. Data analysis revealed that about 25% of patients could participate in the future in (6R)-l-erythro-5, 6, 7, 8-tetrahydrobiopterin (BH₄) treatment trials according to their mutation genotypes. This study enables us to construct a national database in Israel that will serve as a valuable tool for genetic counseling and a prognostic evaluation of future cases of PKU.     

Successful surgical repair of a giant left main coronary artery aneurysm with arteriovenous fistula draining into a persistent left superior vena cava and coronary sinus: role of intraoperative transesophageal echocardiography

We report the case of a 74-year-old woman with a history of hypertension, hypercholesterolemia, and pacemaker who presented to the hospital with new onset New York Heart Association class IV congestive heart failure. Transthoracic echocardiography revealed a markedly dilated right ventricle with normal right ventricular systolic function. There was moderate pulmonary hypertension with an estimated pulmonary artery systolic pressure of 60 mm Hg. Her echocardiogram 1 year earlier had demonstrated normal right ventricular size and systolic function, and no pulmonary hypertension. Additional transthoracic imaging with saline contrast study through a left peripheral vein demonstrated the presence of a dilated coronary sinus with a persistent left superior vena cava. Color Doppler demonstrated turbulent flow within the coronary sinus with evidence of significant left-to-right shunting. Cardiac catheterization revealed a massively dilated left main coronary artery aneurysm with an arteriovenous fistula into the left superior vena cava and coronary sinus. The calculated Qp/Qs was 2:1. The patient underwent 2 unsuccessful attempts at percutaneous intervention to occlude the arteriovenous fistula. She then underwent successful surgical closure of the coronary arteriovenous fistula. The important role of intraoperative transesophageal echocardiography in guiding this technically challenging surgical case is discussed.     

Human embryonic stem cells as an in vitro model for human vascular development and the induction of vascular differentiation

Early embryonic blood vessels are typically composed of fragile tubes of endothelial cells encircled by vascular smooth muscle cells. Early human vasculogenesis was explored in spontaneous and directed differentiation models derived from human embryonic stem (HES) cells. In a 3-dimensional (3D) model, HES cells were studied for their potential for vascular differentiation during the spontaneous formation of embryoid bodies. Directed differentiation was investigated by means of a 2-dimensional (2D) differentiation method to promote vascular differentiation from HES cells (without the formation of embryoid bodies). Using this latter approach, up-regulation of early lineage markers of endothelial progenitors were induced. Additional culture under strict conditions and exposure to angiogenic growth factors resulted in a prolonged differentiation pathway into mature endothelial cells and up-regulation of vascular smooth muscle cell markers. The use of 3D collagen gels and Matrigel assays for the induction and inhibition of human vascular sprouting in vitro further established the vascular potential of the cells generated by the 2D differentiation system. Our study shows that HES cells can provide useful models to study early differentiation and development of blood vessels. Moreover, the 2D differentiation model facilitates both the production of vascular lineage cells from HES cells for various potential therapeutic applications and also provides a model for studying the mechanisms involved in early human embryonic blood vessel development.     

The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency

Background: Dihydrolipoamide dehydrogenase (DLD lipoamide dehydrogenase, the E3 subunit of the pyruvate dehydrogenase complex (PDHC)) is the third catalytic enzyme of the PDHC, which converts pyruvate to acetyl-CoA catalyzed with the introduction of acetyl-CoA to the tricyclic acid (TCA) cycle. In humans, PDHC plays an important role in maintaining glycose homeostasis in an aerobic, energy-generating process. Inherited DLD-E3 deficiency, caused by the pathogenic variants in DLD, leads to variable presentations and courses of illness, ranging from myopathy, recurrent episodes of liver disease and vomiting, to Leigh disease and early death. Currently, there is no consensus on treatment guidelines, although one suggested solution is a ketogenic diet (KD). Objective: To describe the use and effects of KD in patients with DLD-E3 deficiency, compared to the standard treatment. Results: Sixteen patients were included. Of these, eight were from a historical cohort, and of the other eight, four were on a partial KD. All patients were homozygous for the D479V (or D444V, which corresponds to the mutated mature protein without the mitochondrial targeting sequence) pathogenic variant in DLD. The treatment with partial KD was found to improve patient survival. However, compared to a historical cohort, the patients’ quality of life (QOL) was not significantly improved. Conclusions: The use of KD offers an advantage regarding survival; however, there is no significant improvement in QOL.     

Pain and related suffering reduce attention toward others

Background

It has been proposed that the expression of pain-related suffering may lead to an enhanced focus on oneself and reduced attention toward the external world. This study aimed at investigating whether experimentally induced painrelated suffering may lead persons to withdraw into themselves, causing a reduced focus on external stimuli as reflected by impaired performance in a facial recognition task and heightened perception of internal stimuli measured by interoceptive awareness.

Methods

Thirty-two participants had to recognize different emotional facial expressions (neutral, sad, angry, happy), or neutral geometrical figures under conditions of no pain, low, and high prolonged pain intensities. Interoceptive accuracy was measured using a heartbeat-detection task prior to and following the pain protocol.

Results

Males but not females were slower to recognize facial expressions under the condition of high painful stimulation compared to the condition of no pain. In both, male and female participants, the difficulty in recognizing another person's emotions from a facial expression was directly related to the level of suffering and unpleasantness experienced during pain. Interoceptive accuracy was higher after the pain experiment. However, neither the initial interoceptive accuracy nor the change were significantly related to the pain ratings.

Conclusions

Our results suggest that long-lasting and intense painful stimuli, which induce suffering, lead to attentional shifts leading to withdrawal from others. These findings contribute to a better understanding of the social dynamics of pain and pain-related suffering.