Bilateral progressive essential iris atrophy and keratoconus with coincident features of posterior polymorphous dystrophy: a case report and proposed pathogenesis.

We report the first case known to us of an apparent bilateral association of essential iris atrophy (EIA) and keratoconus (KC), with coincident features of posterior polymorphous dystrophy (PPD). Based on this case and the published natural history and findings of both the irido corneal endothelial (ICE) syndrome and PPD, we propose a new hypothesis for the pathogenesis of the ICE syndrome with associated KC and/or PPD. We suggest that, similar to the genetics of retinoblastoma, the predisposition for either the ICE syndrome or for PPD is inherited as an inactive allele, the so-called "first hit." Inactivation of the second allele, or "second hit," which could occur at any time, might be the product of the background mutation rate or of an environmental trigger. Dedifferentiation or an abnormality in normal development could occur after the first or second hit, resulting in varying clinical patterns. We also concur with other investigators that PPD could be part of the spectrum of the ICE syndrome, owing to similarities in their clinical presentations, histopathology, specular and electron microscopy, and natural history.     

Pharmacology of recombinant human GABA(A) receptor subtypes measured using a novel pH-based high-throughput functional efficacy assay

To facilitate the discovery of novel compounds that modulate human GABA(A) receptor function, we have developed a high throughput functional assay using a fluorescence imaging system. L(tk-) cells expressing combinations of human GABA(A) receptor subunits were incubated with the pH-sensitive dye 2',7'bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein, then washed and placed in a 96-well real-time fluorescence plate reader. In buffer adjusted to pH 6.9 there was a robust and persisting acidification response to addition of GABA, which was antagonised by the GABA(A) receptor antagonist bicuculline. The concentration-response relationship for GABA was modulated by allosteric ligands, including benzodiazepine (BZ) site agonists and inverse agonists. The effects of BZ site ligands on the pH response to GABA for receptors containing alpha1beta3gamma2, alpha3beta3gamma2 or alpha5beta3gamma2 subunits were well correlated with results from electrophysiological studies on the same receptor subunit combinations expressed in Xenopus oocytes. Most modulatory compounds tested were found to be relatively unselective across the three subunit combinations tested; however, some showed subtype-dependent efficacy, such as diazepam, which had highest agonist effects on the alpha3beta3gamma2 subtype, substantial but lesser agonism on alpha1beta3gamma2 and still substantial but the least agonism on alpha5beta3gamma2. This indicates that the alpha subunit within the recombinant receptor expressed in L(tk-) cells can affect the efficacy of the response to some BZ compounds. Inhibitors of Na(+)/Cl(-) cotransport, anion/anion exchange and the gastric type of H(+)/K(+) ATPase potently inhibited GABA-evoked acidification, indicating that multiple transporters are involved in the GABA-evoked pH change. This novel fluorescence-based high throughput functional assay allows the rapid characterization of allosteric ligands acting on human GABA(A) receptors.     

Endoscopic KTP-532 laser assisted diverticulotomy for Zenker's diverticulum

Zenker's diverticulum, though counnon in western countries is uncommon in India. This diverticuham is an extension of umcosa through Killian's dehiscence. Various surgical methods have been described for the treatment of this condition including the use of lasers but none in Indian Journals. In this paper we describe a case of Zenker's diverticulum where diverticulotomy using KTP532 laser was successfully performed. Its advantages over other techniques are mentioned.     

Numerical Simulation on Thermal Stresses and Solidification Microstructure for Making Fiber-Reinforced Aluminum Matrix Composites

The fabrication of fiber-reinforced metal matrix composites (MMCs) mainly consists of two stages: infiltration and solidification, which have a significant influence on the properties of MMCs. The present study is primarily focused on the simulation of the solidification process and the effect of the active cooling of fibers with and without nickel coating for making the continuous carbon fiber-reinforced aluminum matrix composites. The thermomechanical finite element model was established to investigate the effects of different cooling conditions on the temperature profile and thermal stress distributions based on the simplified physical model. The predicted results of the temperature distribution agree well with the results of the references. Additionally, a three-dimensional cellular automata (CA) finite element (FE) model is used to simulate the microstructure evolution of the solidification process by using ProCAST software. The results show that adding a nickel coating can make the heat flux smaller in the melt, which is favorable for preventing debonding at the coating/fiber and alloy interface and obtaining a finer microstructure. In the presence of the nickel coating, the number of grains increases significantly, and the average grain size decreases, which can improve the properties of the resultant composite materials. Meanwhile, the predicting results also show that the interfaces of fiber–coating, fiber–melt, and coating–melt experience higher temperature gradients and thermal stresses. These results will lead to the phenomenon of stress concentration and interface failure. Thus, it was demonstrated that these simulation methods could be helpful for studying the solidification of fiber-reinforced MMCs and reducing the number of trial-and-error experiments.     

The Infancy of Infant Pain Research: The Experimental Origins of Infant Pain Denial

Skepticism toward infant pain characterized much of 20th century research and clinical practice, with infant surgery routinely conducted with minimal or no anesthesia into the 1980s. This paper offers a historical exploration of how this view became common by reviewing and analyzing the experimental infant pain research of the 19th and early 20th centuries that contributed to the development of infant pain denial. These experiments used pinprick and electric shock, and the results were generally interpreted as evidence of infants’ underdeveloped pain perception, attributed to their lack of brain maturation. Even clear responses to noxious stimuli were often dismissed as reflex responding. Later these experimental findings were used by anesthesiologists to support the lessened use of anesthesia for infants. Based on the reviewed literature, this paper suggests that 4 interrelated causes contributed to the denial of infant pain: the Darwinian view of the child as a lower being, extreme experimental caution, the mechanistic behaviorist perspective, and an increasing emphasis on brain and nervous system development. Ultimately this history can be read as a caution to modern researchers to be aware of their own biases, the risks of null hypothesis testing, and a purely mechanistic view of infants.PerspectiveThis article reviews the history of 19th and early 20th century infant pain research, tracing how the widely accepted belief that infants could not feel pain developed in the period prior to the growing acceptance of infant pain. Four interrelated causes are posited to help explain the tolerance of infant pain denial until recent times.     

Heterogeneity of B cell involvement in acute nonlymphocytic leukemia

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.     

Femoral neck resorption following hybrid metal-on-metal hip resurfacing arthroplasty: a radiological and biomechanical analysis

Introduction  

With the resurgence of resurfacing hip arthroplasty complications such as femoral neck fracture and thinning have been identified. We therefore conducted a radiological and biomechanical evaluation of factors affecting femoral neck resorption following resurfacing hip arthroplasty (RHA).     

Solid Organ Transplantation From Hepatitis B Virus–Positive Donors: Consensus Guidelines for Recipient Management

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non‐liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti‐HBc+) donors. Organs from anti‐HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non‐liver recipients but is not recommended in immune non‐liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost‐effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.