Improvement in CD 4 counts in HIV positive patients treated with HAART and antitubercular drugs: an observational study from North India

A decrease in CD4 counts in HIV positive patients with concomitant tuberculosis leads to an increase in the morbidity and mortality. Little data exists about the use of antiretroviral drugs along with antitubercular drugs on the improvement in CD4 counts from this part of country. The records of 119 HIV and TB positive patients were obtained from immunodeficiency clinic of tertiary care centre of North India who were on drug treatment for both the diseases and were analysed for demographic profile and effects on CD4 counts. There was a statistically significant improvement in the CD4 counts of the patients as compared to their baseline values mean (SD) as 120.03 (124.1) at visit one to 270.2 (141.3) at visit two (p < 0.01) and 320.9 (184.3) at visit three (p < 0.05). Six patients died during the period of evaluation. Concomitant use of antitubercular drugs with antiretroviral drugs has resulted in a significant improvement in the CD4 counts which is a marker of delay in disease progression.     

GPU-based streaming architectures for fast cone-beam CT image reconstruction and demons deformable registration

This paper shows how to significantly accelerate cone-beam CT reconstruction and 3D deformable image registration using the stream-processing model. We describe data-parallel designs for the Feldkamp, Davis and Kress (FDK) reconstruction algorithm, and the demons deformable registration algorithm, suitable for use on a commodity graphics processing unit. The streaming versions of these algorithms are implemented using the Brook programming environment and executed on an NVidia 8800 GPU. Performance results using CT data of a preserved swine lung indicate that the GPU-based implementations of the FDK and demons algorithms achieve a substantial speedup--up to 80 times for FDK and 70 times for demons when compared to an optimized reference implementation on a 2.8 GHz Intel processor. In addition, the accuracy of the GPU-based implementations was found to be excellent. Compared with CPU-based implementations, the RMS differences were less than 0.1 Hounsfield unit for reconstruction and less than 0.1 mm for deformable registration.     

Nonlinear Protein Binding: Not What You Think

Nonlinear protein binding is traditionally thought of as an increasing fraction unbound with increasing total drug concentration. In the past several years, research into the protein binding of several tetracyclines has shown that an unexpected and counterintuitive phenomenon has been observed, specifically that of decreasing unbound drug fraction with increasing total concentrations of drug over certain concentration ranges. Although several studies of tigecycline have shown the importance calcium and its chelation may play in the protein-drug interaction, the potential clinical implications and relevance have not been explored. Here, we define typical and atypical nonlinear protein binding, overview protein binding theory, and discuss theoretical implications on pharmacokinetics. Using tigecycline as an example, in silico simulations and calculations show how when atypical nonlinear protein binding is not accounted for free drug exposure, and drug tissue penetration may be overestimated. It is important to revisit the impacts of nonlinearity in protein binding on clinical pharmacokinetics and pharmacodynamics, and ultimately, clinical efficacy. Although this phenomenon could potentially warrant clinical dose adjustment for certain compounds, it also presents a potential opportunity to exploit underlying mechanisms to develop new therapies and better understand molecular interactions of xenobiotics within the physiological system.     

Physical and Biochemical Characterization of Chemically Treated Pollen Shells for Potential Use in Oral Delivery of Therapeutics

Allergen-free pollen shells obtained from natural pollen grains have recently attracted attention as microcapsules for oral therapeutic delivery. We have recently developed a chemical treatment method that enables successful retrieval of hollow pollen shells from diverse species. A comprehensive characterization is critical to characterize the effects of chemical treatment which will not only benchmark the pollen treatment process but can also lay the foundation of quality control procedures to check allergen-removal efficiency during pollen treatment. Therefore, in this study, we followed the effects of chemical treatment on 4 different pollen species using electron microscopy, elemental analysis, gel electrophoresis, confocal microscopy, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. These analyses revealed that acetone treatment removed lipids from the pollen surface. Phosphoric acid treatment removed proteins and nucleic acids from the pollen core and transformed esters into carboxylic acids. Potassium hydroxide hydrolysis changed carbohydrate composition of the pollen wall. Chemically treated pollen shells exhibited hydroxyl and carboxyl functional groups on their surface. Overall, we propose that confocal microscopy could be used as a rapid scanning technique to visualize the removal of biomolecules, whereas Fourier-transform infrared combined with gel electrophoresis could be used as a more objective approach for analysis and benchmarking.     

Malignancy in Renal Transplant Recipients Exposed to Cyclophosphamide Prior to Transplantation for the Treatment of Native Glomerular Disease

Study Objective

To evaluate the risk of posttransplantation malignancy in renal transplant recipients exposed to pretransplantation cyclophosphamide for the treatment of glomerular nephropathy (GN).

Design

Retrospective cohort study.

Setting

Tertiary academic medical center.

Patients

Six hundred adult renal transplant recipients were transplanted between 1993 and 2014; 54 patients were exposed to pretransplantation cyclophosphamide for treatment of GN (GN‐CYC group), and 546 patients with polycystic kidney disease were not exposed to pretransplantation cyclophosphamide (PKD group).

Measurement and Main Results

Data were collected retrospectively from electronic medical records. The primary outcome was occurrence of posttransplantation malignancy. During a median follow‐up of 5.5 years, 130 patients developed malignancy (incidence rate 3.5 events per 100 person‐yrs). Exposure to cyclophosphamide before transplantation was significantly associated with malignancy after transplantation (adjusted hazard ratio [aHR] 2.20, 95% confidence interval [CI] 1.16–4.22, p=0.02), specifically skin cancer (aHR 2.24, 95% CI 1.09–4.60, p=0.03). Malignancy risk in the GN‐CYC group was higher in the setting of lymphocyte‐depleting induction (alemtuzumab; aHR 4.53, 95% CI 0.99–20.72, p=0.05) compared with basiliximab induction. Incidences of death‐censored graft loss and mortality were similar between the GN‐CYC and PKD groups.

Conclusion

In our observational study, renal transplant recipients exposed to pretransplantation cyclophosphamide appeared to have a higher risk of developing a malignancy compared with unexposed renal transplant recipients. Further investigation into the impact of pretransplantation immunosuppression on malignancy, particularly the compounded effect with lymphocyte‐depleting induction, is warranted.