23422111
Social deprivation and primary hyperparathyroidism.
OBJECTIVE
To investigate the potential relationship between social status or deprivation and the prevalence of primary hyperparathyroidism (PHPT).


METHODS
We retrospectively identified a cohort of patients diagnosed as having PHPT between 1981 and 2007 from the Scottish Morbidity Records database. The Scottish Index of Multiple Deprivation (SIMD) 2006 quintiles were derived for these patients by using the postal codes. The distribution of the SIMD quintiles was examined to determine the possible influence of deprivation on the incidence of PHPT.


RESULTS
In Scotland between 1981 and 2007, 3,039 patients were diagnosed as having PHPT, in accordance with the International Classification of Diseases code for PHPT. The distribution of the PHPT cohort across the SIMD 2006 quintiles was significantly different from that expected, with a higher representation (27.2%) among the most deprived and a lower representation (14.5%) in the least deprived quintile, in comparison with the 20% expected in each quintile (P<.0001).


CONCLUSION
The findings in this study suggest that socioeconomic deprivation is associated with an increased risk of developing PHPT.
207226533
Interference in free thyroxine immunoassay.
We report two patients who presented with non-specific symptoms of tiredness that prompted their clinician to order a thyroid function test. In both cases, free thyroxine (T4) was reported to be high, with a normal thyroid-stimulating hormone (TSH). Repeated blood tests from the same laboratory using the same assay method yielded similar results. Due to discrepancies between the clinical and laboratory findings, we decided to repeat the blood tests at another laboratory using a different assay method. This revealed normal free T4 and TSH levels, suggesting that heterophile antibodies were interfering with the free T4 assay, leading to clinical confusion.
40019002
Prospective randomized comparative study of macular thickness following phacoemulsification and manual small incision cataract surgery.
PURPOSE
To compare macular thickness following uncomplicated phacoemulsification with foldable acrylic lens and manual small incision cataract surgery (MSICS) with non-foldable polymethyl methacrylate (PMMA) lens implantation.


METHODS
Prospective study was carried out with one eye each of 224 patients with senile cataract randomized into two groups, phacoemulsification and MSICS, by simple 1:1 randomization. Following surgery by either of the two methods, macular thickness was measured by optical coherence tomography (OCT) on the 1st, 7th, 42nd and 180th postoperative day. Main outcome measure was postoperative macular thickness.


RESULTS
On the first postoperative day, central subfield mean thickness (CSMT) in MSICS group was 192.8 +/- 17.9 microm and that in phacoemulsification group was 192.1 +/- 27.4 microm, with no significant difference (p = 0.12). On the 7th day, CSMT in MSICS group (198.9 +/- 21.4 microm) was significantly (p = 0.04) more than that in phacoemulsification group (193.1 +/- 19.3 microm). On the 42nd day, CSMT in MSICS group was 207.8 +/- 26.3 microm and that in phacoemulsification group was 198.3 +/- 23 microm, the difference being significant (p = 0.007). Clinically macular oedema was not diagnosed in any of the patients at any visit. The increase in macular thickness was sub-clinical and did not affect final visual outcome in any patient.


CONCLUSION
In spite of the greater theoretical risk of increased postoperative inflammation following MSICS, there was no evidence of cystoid macular oedema, either clinically or on OCT. However, chance of sub-clinical increase in CSMT was more following MSICS compared to phacoemulsification.
24420829
Why is sodium cocoyl isethionate (SCI) mild to the skin barrier? - An in vitro investigation based on the relative sizes of the SCI micelles and the skin aqueous pores.
Sodium cocoyl isethionate (SCI) is an important surfactant ingredient in mild, syndet (synthetic detergent) cleansing bars. In vitro and in vivo studies have demonstrated that SCI is mild and less damaging to the skin barrier than soaps and surfactants such as sodium dodecyl sulfate (SDS). We have recently shown that SDS forms small micelles in aqueous solutions contacting the skin relative to the aqueous pores in the stratum corneum (SC), and as a result, the SDS micelles can contribute to SDS skin penetration and induce skin barrier perturbation. In this paper, we attempt to explain the well-documented skin mildness of SCI by examining the size of the SCI micelles relative to that of the aqueous pores in the SC. For this purpose, we have conducted in vitro mannitol skin permeability and average skin electrical resistivity measurements upon exposure of the skin to an aqueous SCI contacting solution in the context of a hindered-transport aqueous porous pathway model of the SC. These in vitro studies demonstrate that an SCI micelle of radius 33.5 +/- 1 Angstrom (as determined using dynamic light-scattering measurements) experiences significant steric hindrance and cannot penetrate into the SC through aqueous pores that have an average radius of 29 +/- 5 Angstrom. We believe that this inability of the SCI micelles to contribute to SCI skin penetration and associated skin barrier perturbation is responsible for the observed skin mildness of SCI. Through in vitro quantitative skin radioactivity assays using (14)C-radiolabeled SCI and pig full-thickness skin (p-FTS), we also show conclusively that SCI skin penetration is dose-independent, an important finding that provides additional evidence that the larger SCI micelles cannot penetrate into the SC through the smaller aqueous pores that exist in the SC, and therefore, cannot induce skin barrier perturbation.
43633481
Interactions of Escherichia coli thioredoxin, the processivity factor, with bacteriophage T7 DNA polymerase and helicase.
Escherichia coli thioredoxin binds to a unique flexible loop of 71 amino acid residues, designated the thioredoxin binding domain (TBD), located in the thumb subdomain of bacteriophage T7 gene 5 DNA polymerase. The initial designation of thioredoxin as a processivity factor was premature. Rather it remodels the TBD for interaction with DNA and the other replication proteins. The binding of thioredoxin exposes a number of basic residues on the TBD that lie over the duplex region of the primer-template and increases the processivity of nucleotide polymerization. Two small solvent-exposed loops (loops A and B) located within TBD electrostatically interact with the acidic C-terminal tail of T7 gene 4 helicase-primase, an interaction that is enhanced by the binding of thioredoxin. Several basic residues on the surface of thioredoxin in the polymerase-thioredoxin complex lie in close proximity to the TBD. One of these residues, lysine 36, is located proximal to loop A. The substitution of glutamate for lysine has a dramatic effect on the binding of gene 4 helicase to a DNA polymerase-thioredoxin complex lacking charges on loop B; binding is decreased 15-fold relative to that observed with wild-type thioredoxin. This defective interaction impairs the ability of T7 DNA polymerase-thioredoxin together with T7 helicase to mediate strand displacement synthesis. This is the first demonstration that thioredoxin interacts with replication proteins other than T7 DNA polymerase.
21178390
Natalizumab for active Crohn's disease.
BACKGROUND
In chronic inflammatory conditions such as Crohn's disease, the migration of leukocytes from the circulation into the parenchyma and their activation within inflammatory sites are mediated in part by alpha4 integrins.


METHODS
We conducted a double-blind, placebo-controlled trial of the alpha4 integrin-specific humanized monoclonal antibody natalizumab in 248 patients with moderate-to-severe Crohn's disease. Patients were randomly assigned to receive one of four treatments: two infusions of placebo; one infusion of 3 mg of natalizumab per kilogram of body weight, followed by placebo; two infusions of 3 mg of natalizumab per kilogram; or two infusions of 6 mg of natalizumab per kilogram. Infusions were given four weeks apart. Outcomes included changes in scores for the Crohn's Disease Activity Index (higher scores indicate more severe disease), the health-related quality of life, and C-reactive protein levels.


RESULTS
The group given two infusions of 6 mg of natalizumab per kilogram did not have a significantly higher rate of clinical remission (defined by a score of less than 150 on the Crohn's Disease Activity Index) than the placebo group at week 6 (the prospectively defined primary end point in the efficacy analysis). However, both groups that received two infusions of natalizumab had higher remission rates than the placebo group at multiple time points. Natalizumab also produced a significant improvement in response rates (defined by a reduction of at least 70 points in the score on the Crohn's Disease Activity Index). The highest remission rate was 44 percent and the highest response rate was 71 percent (at week 6 in the group given two infusions of 3 mg per kilogram). Overall, the two infusions of 6 mg of natalizumab per kilogram and of 3 mg per kilogram had similar effects. The quality of life improved in all natalizumab groups; C-reactive protein levels improved in groups receiving two infusions of natalizumab. The rates of adverse events were similar in all four groups.


CONCLUSIONS
Treatment with the selective adhesion-molecule inhibitor natalizumab increased the rates of clinical remission and response, improved the quality of life and C-reactive protein levels, and was well tolerated in patients with active Crohn's disease.
40815524
Constrained photophysics of partially and fully encapsulated charge transfer probe (E)-3-(4-Methylaminophenyl) acrylic acid methyl ester inside cyclodextrin nano-cavities: evidence of cyclodextrins cavity dependent complex stoichiometry.
The polarity sensitive intra-molecular charge transfer (ICT) emission from (E)-3-(4-Methylaminophenyl) acrylic acid methyl ester (MAPAME) is found to show distinct changes once introduced into the nano-cavities of cyclodextrins in aqueous environment. Movement of the molecule from the more polar aqueous environment to the less polar, hydrophobic cyclodextrin interior is marked by the blue shift of the CT emission band with simultaneous fluorescence intensity enhancement. The emission spectral changes on complexation with the α- and β-CD show different stoichiometries as observed from the Benesi-Hildebrand plots. Fluorescence anisotropy and lifetime measurements were performed to probe the different behaviors of MAPAME in aqueous α- and β-CD solutions.