Surgical management of multivalvular heart disease

Background This study of patients with multivalvular lesions was undertaken to assess optimal surgical management and identify risk factors for prognosis. Methods Five hundred and twenty one patients underwent valve repair or replacement surgery between January’90 and December’98. Mean age was 30.19±12.2 years and 342 were males. All patients had dyspnoea on exertion, 467 (89.6%) were in New York Heart Association (NYHA) Class III and 47 (9.0%) were in Class IV. Congestive Heart Failure in 67 (12.3%) and prior cardiac procedure in 66 (12.2%) were other risk factors. The valves affected were mitral and aortic in 483 (Group 1), mitral and tricuspid in 43 (Group II) and mitral, aortic and tricuspid in 40 (Group III) patients. Surgical procedures included, several different combinations using repair or replacement with prosthetic or biological substitutes. Results Operative mortality was 9.8% (51 patients). Follow up (1 to 108 months, mean 45 months) was 94% complete. Late mortality occurred in 48 patients (10.4%). Causes included, left ventricular dysfunction (n=21), valve thrombosis (n=10) and, endocarditis (n=8). Freedom from late events was 50.7±8.5% at 9 years. At their last visit 40 patients were in Class IV, 18 were in Class III, 59 in Class II and the remaining in Class I (NYHA). Conclusions Important predictors of early mortality were NYHA Class IV, congestive heart failure, tricuspid valve disease and prior cardiac surgery. Left ventricular dysfunction was an important determinant of late outcome.     

Photohuperzine A—A new photoisomer of huperzine A: Structure elucidation,formation kinetics and activity assessment

A new photoisomer of the promising “anti-Alzheimer” drug candidate (±) huperzine A is described. The new substance was formed via a photoisomerization reaction and was found to be 1-amino-13-ethylidene-11-methyl-6-aza-tetracyclo-[7.3.1.0^2.7.0^4.7]-trideca-2,10-diene-5-one using NMR analysis. The kinetics of its formation was studied and proven to be of first-order. The described photoisomer showed a significant loss in activity, being more than 100 times less active than (−) huperzine A itself. The new substance was named photohuperzine A, referring to its photopyridone substructure.     

Serum proteomics and disease-specific biomarkers of patients with advanced gastric cancer

Gastric cancer is a commonly diagnosed solid tumor which is associated with a dismal prognosis making early diagnosis essential. Thus, this study aimed to identify novel biomarkers in gastric cancer. Serum of patients with advanced gastric cancer was collected according to a predefined schedule: prior to first-line chemotherapy with epirubicin (50 mg/m(2), day 1), cisplatin (60 mg/m(2), day 1) and capecitabine (1,000 mg/m(2), twice daily on days 1-14). The serum was collected serially before the treatment cycles and then analyzed by SELDI-TOF MS. Normal control subjects were matched according to age, gender and serum collection. Serum proteomic mass spectrometry data of all subjects were processed using the tbimass R-package and compared. We analyzed i) whether proteomic profile changes were associated with a response to chemotherapy and survival, and ii) whether changes in proteomic profiles occurring during the time period of chemotherapy were associated with tumor response. In total, 82 patients with adenocarcinoma of the stomach (mean age 57 years, males 69.5%) were treated with a mean number of five chemotherapy cycles. The overall tumor response rate, complete and partial remission combined, was 37%, median time to progression was 7 months (95% CI, 6-8) and median overall survival 11 months (95% CI, 9.5-12). By comparing 77 serum samples of patients with normal matched controls, we identified 32 proteins which discriminated the two groups. By selecting the most differentiating proteins, we built a classification model that correctly categorized 81% of the gastric cancer patients and 90% of the normal controls. Furthermore, we found a statistically significant correlation between the pre-treatment intensity of serum amyloid-α (SAA) and overall survival in gastric cancer patients, whereby a low intensity of SAA predicted a longer patient survival. A classification model, based on the 32 most discriminating proteins differentiating gastric cancer from normal controls, correctly classified subjects with relatively high sensitivity and specificity.     

Early cognitive impairment: Role of clock drawing test

Background: Folstein's Mini Mental Status Examination (MMSE) often fails to identify executive dysfunction even if quite severe. Detailed neuropsychological tests and extensive bedside tests are available to evaluate executive function, but most of them are time consuming. This study was done to determine the value of a Clock Drawing Test (CDT) as a simple tool to identify cognitive dysfunction in various neurological disorders and to assess its utility as an adjunct to MMSE in identifying executive dysfunction in a a busy out patient department (OPD).     

Lymphatic drainage from the treated versus untreated prostate: feasibility of sentinel node biopsy in recurrent cancer

Purpose  

The goal of this study was to establish the feasibility of sentinel node biopsy in patients with recurrent prostate cancer after initial local treatment and to compare lymphatic drainage patterns of the treated versus untreated prostate.     

Functional capacity and actual daily activity do not contribute to patient satisfaction after total knee arthroplasty

Background  

After total knee arthroplasty (TKA) only 75-89% of patients are satisfied. Because patient satisfaction is a prime goal of all orthopaedic procedures, optimization of patient satisfaction is of major importance. Factors related to patient satisfaction after TKA have been explored, but no studies have included two potentially relevant factors, i.e. the functional capacity of daily activities and actual daily activity. This present prospective study examines whether functional capacity and actual daily activity (in addition to an extensive set of potential factors) contribute to patient satisfaction six months after TKA.     

Flexible and Scalable Full‐Length CYP2D6 Long Amplicon PacBio Sequencing

Cytochrome P450 2D6 (CYP2D6) is among the most important genes involved in drug metabolism. Specific variants are associated with changes in the enzyme's amount and activity. Multiple technologies exist to determine these variants, like the AmpliChip CYP450 test, Taqman qPCR, or Second‐Generation Sequencing, however, sequence homology between cytochrome P450 genes and pseudogene CYP2D7 impairs reliable CYP2D6 genotyping, and variant phasing cannot accurately be determined using these assays. To circumvent this, we sequenced CYP2D6 using the Pacific Biosciences RSII and obtained high‐quality, full‐length, phased CYP2D6 sequences, enabling accurate variant calling and haplotyping of the entire gene‐locus including exonic, intronic, and upstream and downstream regions. Unphased diplotypes (Roche AmpliChip CYP450 test) were confirmed for 24 of the 25 samples, including gene duplications. Cases with gene deletions required additional specific assays to resolve. In total, 61 unique variants were detected, including variants that had not previously been associated with specific haplotypes. To further aid genomic analysis using standard reference sequences, we have established an LOVD‐powered CYP2D6 gene‐variant database, and added all reference haplotypes and data reported here. We conclude that our CYP2D6 genotyping approach produces reliable CYP2D6 diplotypes and reveals information about additional variants, including phasing and copy‐number variation.     

Systemic and immunotoxicity of silver nanoparticles in an intravenous 28 days repeated dose toxicity study in rats

Because of its antibacterial activity nanosilver is one of the most commonly used nanomaterials. It is increasingly used in a variety of both medical and consumer products resulting in an increase in human exposure. However, the knowledge on the systemic toxicity of nanosilver is relatively limited. To determine the potential systemic toxicity of silver nanoparticles (Ag-NP) with different sizes (20 nm and 100 nm) a 28-days repeated dose toxicity study was performed in rats using intravenous administration. The toxic effect of the 20 nm Ag-NP was performed using the bench mark dose (BMD) approach.