Trial of pyrethroid impregnated bednets in an area of Tanzania holoendemic for malaria. Part 1. Operational methods and acceptability.

In five Tanzanian villages, nets impregnated with permethrin or lambdacyhalothrin were given out. The people received them enthusiastically and brought their nets for re-impregnation at six monthly intervals. Bioassays showed that the insecticidal power of permethrin impregnated nets remained adequate for six months unless the nets were washed. Nets with 30 mg lambdacyhalothrin/m2 retained high insecticidal power despite washing, but this dose caused temporary cold-like symptoms in those sleeping under freshly treated dry nets. Methods by which durable bednets might be made affordable by Tanzanian villagers are discussed.     

Central core disease. Report of 2 cases in adults

"Central core disease" (CCD) is a rare disease of infancy and childhood and represents the prototypic member of a group of muscular disorders known as "congenital, benign (non progressive) myopathies". It is very uncommon to diagnose cases affected by CCD in youth and adulthood. The disease is mainly familial with a dominant autosomal pattern of inheritance, but sporadic cases are known to occur. The candidate gene has been localized on chromosome 19q13.1, and is allelic with RYR-1 ("ryanodine receptor" [calcium release channel gene]), the gene responsible of the susceptibility to malignant hyperthermia. In some familial cases of CCD a susceptibility to malignant hyperthermia was also recognized. The diagnosis is only made based on muscular biopsy, which documents some peculiar morphological abnormalities, i.e. focal losses of oxidative enzyme activities, exclusively in type I muscular fibres. The basis for the loss of such activities is represented by an almost total absence of mitochondria and sarcoplasmic reticulum in those focal regions of muscle fibres. Cores may be "structured" and "unstructured" based on the reactivity with myosin ATPases, which ultrastructurally means preservation or destruction of myofilaments. Both structured and unstructured cores qualify this disease in the same way. The authors have observed two cases of CCD in patients in their non infantile age. Both diagnoses were accomplished by means of muscular biopsy, and the results of their studies in both cases are herein presented and discussed.     

Capsule endoscopy:Present status and future expectation

Video capsule endoscopy(CE)since its introduction 13years back,has revolutionized our approach to small intestinal diseases.Obscure gastrointestinal bleed(OGIB)continues to be the most important indication for CE with a high sensitivity,specificity as well as positive and negative predictive values.It is best performed during ongoing bleed or immediately thereafter.Overt OGIB has a higher diagnostic yield than occult OGIB.However,even in iron deficiency anemia,CE is emerging as important investigation after initial negative work up.In suspected Crohn’s disease(CD),CE has been shown superior to traditional imaging and endoscopic technique and should be considered after a negative ileocolonoscopy.Although CE has also been used for evaluating established CD,a high capsule retention rate precludes its use ahead of cross-sectional imaging.Celiac disease,particularly where gastro-duodenoscopy cannot be performed or is normal,can also be investigated by CE.Small bowel tumor,hereditary polyposis syndrome,and non-steroidal anti-inflammatory drugs induced intestinal damage are other indications for CE.Capsule retention is the only significant adverse outcome of CE and occurs mostly in presence of intestinal obstruction.This can be prevented by use of Patency capsule prior to CE examination.Presence of cardiac pacemaker and intracardiac devices continue to be relative contraindications for CE,though data do not suggest interference of CE with these devices.Major limitations of CE today include failure to control its movement from outside,inability of CE to acquire tissue for diagnosis,and lack of therapeutic help.With ongoing interesting and exciting developments taking place in these areas,these issues would be solved in all probability in near future.CE has the potential to become one of the most important tools in diagnostic and possibly in the therapeutic field of gastrointestinal disorder.     

Development of a Magnetic Attachment Method for Bionic Eye Applications

Successful visual prostheses require stable, long‐term attachment. Epiretinal prostheses, in particular, require attachment methods to fix the prosthesis onto the retina. The most common method is fixation with a retinal tack; however, tacks cause retinal trauma, and surgical proficiency is important to ensure optimal placement of the prosthesis near the macula. Accordingly, alternate attachment methods are required. In this study, we detail a novel method of magnetic attachment for an epiretinal prosthesis using two prostheses components positioned on opposing sides of the retina. The magnetic attachment technique was piloted in a feline animal model (chronic, nonrecovery implantation). We also detail a new method to reliably control the magnet coupling force using heat. It was found that the force exerted upon the tissue that separates the two components could be minimized as the measured force is proportionately smaller at the working distance. We thus detail, for the first time, a surgical method using customized magnets to position and affix an epiretinal prosthesis on the retina. The position of the epiretinal prosthesis is reliable, and its location on the retina is accurately controlled by the placement of a secondary magnet in the suprachoroidal location. The electrode position above the retina is less than 50 microns at the center of the device, although there were pressure points seen at the two edges due to curvature misalignment. The degree of retinal compression found in this study was unacceptably high; nevertheless, the normal structure of the retina remained intact under the electrodes.     

Optical Coherence Tomography‐Guided Retinal Prosthesis Design: Model of Degenerated Retinal Curvature and Thickness for Patient‐Specific Devices

Retinitis pigmentosa affects over 1.5 million people worldwide and is a leading cause of vision loss and blindness. While retinal prostheses have shown some success in restoring basic levels of vision, only generic, “one‐size‐fits‐all” devices are currently being implanted. In this study, we used optical coherence tomography scans of the degenerated retina from 88 patients with retinitis pigmentosa to generate models of retinal thickness and curvature for the design of customized implants. We found the average retinal thickness at the fovea to be 152.9 ± 61.3 μm, increasing to a maximum retinal thickness of 250.9 ± 57.5 μm at a nasal eccentricity of 5°. These measures could be used to assist the development of custom‐made penetrating electrodes to enhance and optimize epiretinal prostheses. From the retinal thickness measurements, we determined that the optimal length of penetrating electrodes to selectively stimulate retinal ganglion cell bodies and interneuron axons in the ganglion cell layer should be 30–100 μm, and to preferentially stimulate interneurons in the inner nuclear layer, electrodes should be 100–200 μm long. Electrodes greater than 200 μm long had the potential to penetrate through the retina into the choroid, which could cause devastating complications to the eye and should be avoided. The two‐ and three‐dimensional models of retinal thickness developed in this study can be used to design patient‐specific epiretinal implants that will help with safety and to optimize the efficacy of neuronal stimulation, ensuring the best functional performance of the device for patients.     

Serum S-100beta as a possible marker of blood-brain barrier disruption

Two brain-specific proteins, S-100β and neuron-specific enolase (NSE), are released systemically after cerebral lesions, but S-100β levels sometimes rise in the absence of neuronal damage. We hypothesized that S-100β is a marker of blood–brain barrier (BBB) leakage rather than of neuronal damage. We measured both proteins in the plasma of patients undergoing iatrogenic BBB disruption with mannitol, followed by chemotherapy. Serum S-100β increased significantly after mannitol infusion (P<0.05) while NSE did not. This suggests that S-100β is an early marker of BBB opening that is not necessarily related to neuronal damage.     

New measles genotype, Uganda

We report the first genetic characterization of wildtype measles viruses from Uganda. Thirty-six virus isolates from outbreaks in 6 districts were analyzed from 2000 to 2002. Analyses of sequences of the nucleoprotein (N) and hemagglutinin (H) genes showed that the Ugandan isolates were all closely related, and phylogenetic analysis indicated that these viruses were members of a unique group within clade D. Sequences of the Ugandan viruses were not closely related to any of the World Health Organization reference sequences representing the 22 currently recognized genotypes. The minimum nucleotide divergence between the Ugandan viruses and the most closely related reference strain, genotype D2, was 3.1% for the N gene and 2.6% for the H gene. Therefore, Ugandan viruses should be considered a new, proposed genotype (d10). This new sequence information will expand the utility of molecular epidemiologic techniques for describing measles transmission patterns in eastern Africa.     

The Safety and Efficacy of Single‐Agent Pemetrexed in Platinum‐Resistant Advanced Urothelial Carcinoma: A Large Single‐Institution Experience

Background.

Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance.

Patients and Methods.

Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded.

Results.

One hundred and twenty-nine patients were treated with pemetrexed. The objective response rate was 5% (95% confidence interval: 1%–9%), and the median duration of response was 8 months. Median progression-free survival (PFS) was 2.4 months, and the 6-month PFS rate was 14%. There was no significant difference in response rate by age, Eastern Cooperative Oncology Group (ECOG) performance status, or number of prior therapies. On multivariable analysis, ECOG performance status (p < .01), liver metastases (p = .02), and NLR (p < .01) had independent prognostic significance for overall survival.

Conclusion.

This 129-patient series is the largest reported data set describing pemetrexed use in advanced UC. Activity was modest, although discovery of molecular biomarkers predictive of response would be valuable to identify the small subset of patients who do gain significant benefit. Overall, the data highlight the urgent need to develop novel therapies for these patients.