Incremental value of live/real time three-dimensional echocardiography in the diagnosis and evaluation of pericardial cyst

Pericardial cysts are rare anomalies of the pericardium that are usually asymptomatic and followed by two-dimensional (2D) echocardiography. Here we report a large pericardial cyst that could not be measured accurately by 2D echocardiography but three-dimensional (3D) echocardiography enabled measurements of the cyst that correlated well with computed tomography measurements. In addition, 3D echocardiography demonstrated the mono-trabeculated nature of the cyst further suggesting the incremental value of 3D echocardiography in the evaluation of pericardial cysts. The cyst was subsequently resected surgically.     

Live/real time three-dimensional transthoracic echocardiographic assessment of the involvement of cardiac valves and chambers in carcinoid disease

We present an adult with metastatic carcinoid disease affecting the heart, in whom live/real time three-dimensional transthoracic echocardiography (3DTTE) provided incremental value over two-dimensional transthoracic echocardiography (2DTTE). Initial 2DTTE was able to demonstrate severe pulmonic and tricuspid regurgitation, but was unable to visualize the posterior leaflet of the tricuspid valve or the right (right anterior) leaflet of the pulmonic valve. Further analysis with 3DTTE demonstrated thickening, restricted mobility, and noncoaptation of all three leaflets of both the tricuspid and the pulmonary valves. En face viewing of tricuspid and pulmonary regurgitation vena contractas permitted more reliable quantification of regurgitation severity. In addition, localized, linear, echogenic areas consistent with carcinoid deposits were noted along the inner walls of the right atrium, atrial septum, and inferior vena cava. To the best of our knowledge, endocardial carcinoid deposits have never been reported by 2D or 3D echocardiography. En face viewing of these deposits by 3DTTE enabled measurement of their dimensions and areas. Subcostal examination also identified large circumscribed hepatic lesions consistent with metastatic disease. Neither the carcinoid deposits nor the metastatic lesions were detected by 2DTTE. This case demonstrates the usefulness of 3DTTE as a supplement to 2DTTE in more comprehensively assessing carcinoid involvement of the heart.     

Discharge disposition after pancreatic resection for malignancy: analysis of national trends

Objectives

The aim of this study is to analyse national trends in discharge disposition following pancreatic resection for malignancy in the USA.

Methods

The Nationwide Inpatient Sample database was queried for 1993–2005 to identify patients who underwent pancreatic resection for malignancy. The status of patients at discharge (to home, home with home health care or to another facility) was noted.

Results

A weighted total of 51 866 patients who underwent pancreatectomy for malignant neoplasm of the pancreas were identified. Patients who died in the postoperative period and patients without a specified discharge disposition were excluded, leaving 43 603 patients for inclusion in the study. Overall mortality improved over the period of the study from 7.1% in 1993 to 5.2% in 2005. The number of patients discharged to another facility increased significantly from 5.5% in 1993 to 13.3% in 2005. Similarly, the number of patients discharged to home with home health assistance increased from 20.0% in 1993 to 33.0% in 2005. This corresponded with a statistically significant decrease in the number of patients discharged to home without assistance, from 74.5% in 1993 to 53.7% in 2005 (P= 0.002).

Conclusions

The results of our study demonstrate that following pancreatic resection for malignancy, nearly half the patients will require some assistance after discharge.     

Surgical patterns in osteoporotic vertebral compression fractures

Purpose

To report morphological patterns of osteoporotic vertebral compression fractures (OVCFs) presenting for surgery. To describe surgical options based on fracture pattern. To evaluate clinical and radiological outcome.

Methods

Forty consecutively operated OVCFs nonunion patients were retrospectively studied. We define four patterns of OVCFs that needed surgical intervention. Group 1 mini open vertebroplasty (N = 10) no neurologic deficits and kyphotic deformity, but with intravertebral instability and significant radiological spinal canal compromise. Group 2 with neurologic deficits (N = 24) (2A)—transpedicular decompression (TPD) with instrumentation (N = 14). Fracture morphology similar to (1) and localized kyphosis <30° (2B)—pedicle subtraction osteotomy (PSO) with instrumentation (N = 10). Fracture morphology similar to (1) and local kyphosis >30°. Group 3 posterolateral decompression with interbody reconstruction (N = 06) endplate(s) destroyed, with instability at discovertebral junction, with neurologic deficit. Average follow-up was 34 months. VAS, ODI and Cobb angle were recorded at 3, 6, 12 months and yearly.

Results

There was significant improvement in the clinical (VAS and ODI) scores and radiologic outcome in each group at last follow-up. 30 patients out of 40, had neurologic deficits (Frankel’s grade C = 16, Frankel’s grade D = 14). The motor power gradually improved to Frankel’s grade E. Average duration of surgery was 97 min. Average blood loss was 610 ml.

Conclusion

Different surgical techniques were used to suit different fracture patterns, with good clinical and radiological results. This could be a step forward in devising an algorithm to surgical treatment of OVCF nonunions.     

Statistical mechanics of convergent evolution in spatial patterning

We explore how the genotype–phenotype map determines convergent evolution in a simple model of spatial gene regulation during development. Evolution is simulated via a Monte Carlo scheme that incorporates mutation, selection, and genetic drift, by using a bottom-up model of gene regulation with a fitness function that is optimized by a switch-like response to a morphogen gradient. We find that even for very simple regulation, the genotype–phenotype map gives rise to an emergent fitness landscape of remarkable complexity. This leads to a richness of evolutionary behavior as population size is increased that parallels the thermodynamics of physical systems as temperature decreases. Convergence is controlled by the existence of sufficiently dominant global optima in “free fitness,” which is a quantity that is the balance of mutational entropy and fitness. In independent simulations at low population sizes, we find convergence to a phenotype of suboptimal fitness due to the multiplicity or entropy of solutions. This contrasts with convergence to the optimal fitness phenotype at high population size. However, at sufficiently large population sizes, we find convergence in only the phenotypes with greatest effect on fitness, whereas noncritical phenotypes exhibit divergence due to quenched disorder on a locally rough landscape. Our results predict that for large populations, the evolution of even simple gene regulatory circuits may be glassy-like, such that, counter to the commonly accepted view that conservation implies function, many conserved phenotypes are simply frozen accidents of little consequence to the fitness of the organism.     

Chemometrics-Assisted UV Spectrophotometric and RP-HPLC Methods for the Simultaneous Determination of Tolperisone Hydrochloride and Diclofenac Sodium in their Combined Pharmaceutical Formulation

Chemometrics-assisted UV spectrophotometric and RP-HPLC methods are presented for the simultaneous determination of tolperisone hydrochloride (TOL) and diclofenac sodium (DIC) from their combined pharmaceutical dosage form. Chemometric methods are based on principal component regression and partial least-square regression models. Two sets of standard mixtures, calibration sets, and validation sets were prepared. Both models were optimized to quantify each drug in the mixture using the information included in the UV absorption spectra of the appropriate solution in the range 241–290 nm with the intervals λ = 1 nm at 50 wavelengths. The optimized models were successfully applied to the simultaneous determination of these drugs in synthetic mixture and pharmaceutical formulation. In addition, an HPLC method was developed using a reversed-phase C18 column at ambient temperature with a mobile phase consisting of methanol:acetonitrile:water (60:30:10 v/v/v), pH-adjusted to 3.0, with UV detection at 275 nm. The methods were validated in terms of linearity, accuracy, precision, sensitivity, specificity, and robustness in the range of 3–30 μg/mL for TOL and 1–10 μg/mL for DIC. The robustness of the HPLC method was tested using an experimental design approach. The developed HPLC method, and the PCR and PLS models were used to determine the amount of TOL and DIC in tablets. The data obtained from the PCR and PLS models were not significantly different from those obtained from the HPLC method at 95% confidence limit.     

Histone deacetylase inhibitor treatment induces ‘BRCAness’ and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells

There is an unmet need to develop new, more effective and safe therapies for the aggressive forms of triple negative breast cancers (TNBCs). While up to 20% of women under 50 years of age with TNBC harbor germline mutations in BRCA1, and these tumors are sensitive to treatment with poly(ADP) ribose polymerase inhibitors, a majority of TNBCs lack BRCA1 mutations or loss of expression. Findings presented here demonstrate that by attenuating the levels of DNA damage response and homologous recombination proteins, pan-histone deacetylase inhibitor (HDI) treatment induces ‘BRCAness’ and sensitizes TNBC cells lacking BRCA1 to lethal effects of PARP inhibitor or cisplatin. Treatment with HDI also induced hyperacetylation of nuclear hsp90. Similar effects were observed following shRNA-mediated depletion of HDAC3, confirming its role as the deacetylase for nuclear HSP90. Furthermore, cotreatment with HDI and ABT-888 induced significantly more DNA strand breaks than either agent alone, and synergistically induced apoptosis of TNBC cells. Notably, co-treatment with HDI and ABT-888 significantly reduced in vivo tumor growth and markedly improved the survival of mice bearing TNBC cell xenografts. These findings support the rationale to interrogate the clinical activity of this novel combination against human TNBC, irrespective of its expression of mutant BRCA1.