A feasibility study of a prototype PET insert device to convert a general-purpose animal PET scanner to higher resolution.

We developed a prototype system to evaluate the feasibility of using a PET insert device to achieve higher resolution from a general-purpose animal PET scanner. METHODS: The system consists of a high-resolution PET detector, a computer-controlled rotation stage, and a custom mounting plate. The detector consists of a cerium-doped lutetium oxyorthosilicate array (12 x 12 crystals, 0.8 x 1.66 x 3.75 mm(3) each) directly coupled to a position-sensitive photomultiplier tube (PS-PMT). The detector signals were fed into the scanner electronics to establish coincidences between the 2 systems. The detector was mounted to a rotation stage that is attached to the scanner via the custom mounting plate after removing the transmission source holder. The rotation stage was concentric with the center of the scanner. The angular offset of the insert detector was calibrated via optimizing point-source images. In all imaging experiments, coincidence data were collected from 9 angles to provide 180 degrees sampling. A (22)Na point source was imaged at different offsets from the center to characterize the in-plane resolution of the insert system. A (68)Ge point source was stepped across the axial field of view to measure the sensitivity of the system. A 23.2-g mouse was injected with 38.5 MBq of (18)F-fluoride and imaged at 3 h after injection for 2 h. RESULTS: The transverse image resolution of the PET insert device ranges from 1.1- to 1.4-mm full width at half maximum (FWHM) without correction for the point-source dimension. This corresponds to approximately 33% improvement over the resolution of the original scanner (1.7- to 1.8-mm FWHM) in 2 of the 3 directions. The sensitivity of the device is 0.064% at the center of the field, 46-fold lower than the sensitivity of an existing animal PET scanner. The mouse bone scan had improved image resolution using the PET insert device over that of the existing animal PET scanner alone. CONCLUSION: We have demonstrated the feasibility of using a high-resolution insert device in an existing PET scanner to provide high-resolution PET. A PET insert device with more detector modules will improve sensitivity and may become an alternative to special-purpose PET systems for high-resolution PET.     

Bedsores: “top to bottom” and “bottom to top”

Bedsore is a global problem concerning the bedridden, infirm, debilitated and malnourished patients in hospitals and community setups. The cost of treatment is enormous involving billions of dollars to nations and individuals. Mortality increases two to six times if bedsores are present. There is little research done despite its commonness to understand how they occur or why they occur; etiology is not much understood. The two theories called ‘top to bottom’ and ‘bottom to top’ contradict each other. It is thought that ‘pressure’, shear-stress’ and ‘ischemia’ may be causing it in some yet to be understood way. There is little awareness on how to prevent them or how to treat them if they do occur. Seldom applied, various scales exist and should be used to identify patients at high risk. Braden scale is the most tested and widely accepted scale. The various available dressings and pressure relief devices are mostly inadequately studied; which is superior is a question that begs an answer. This article aims to underline the importance of bedsores by reviewing our current and past knowledge with emphasis on practical implications thereof.     

Magnetic resonance imaging (MRI) of feet demonstrates subclinical inflammatory joint disease in cutaneous psoriasis patients without clinical arthritis

We evaluated inflammation at the small joints of feet in psoriasis patients without clinical arthritis (PsO) as against clinically overt psoriatic arthritis (PsA) patients, using a low field magnet extremity MRI (eMRI). Patients with psoriasis recruited from dermatology and rheumatology clinics of a tertiary care institution in southern India were divided into PsO and PsA groups. Demographic and physical examination details were recorded. Consenting patients underwent non-contrast eMRI of the right foot. Two trained readers scored the MRI parameters of inflammation (synovitis, tenosynovitis, osteitis) using a modification of the PsA magnetic resonance imaging score (PsAMRIS). Proportion of patients with any sign of MRI inflammation was noted. Clinical variables were compared with inflammation scores for any association. A total of 83 patients (30 PsA and 53 PsO), with 75% males and mean age of 42.2 ± 11.6 years were included. There was no statistical difference between the median eMRI inflammatory scores in PsA and PsO patients (p = 0.493). Evidence of inflammation was present in 33.9% and 50% patients in the PsO and PsA groups, respectively. Early arthritis for psoriatic patients screening questionnaire (EARP) score of ≥ 3 was significantly associated with imaging features of inflammation in PsO group (p = 0.044). This study corroborates a high proportion of subclinical inflammation in small joints of foot in PsO patients, which needs to be reproduced in larger, longitudinal cohorts to predict risk factors for progression to future PsA development.     

Myringoplasty: Impact of Size and Site of Perforation on the Success Rate

Myringoplasty aims to reconstruct the tympanic membrane, restoring protection to the middle ear and improve hearing. Success of Myringoplasty in terms of anatomical closure is influenced by many factors. This study focuses on the influence of size and site of tympanic membrane perforation on success rate of Myringoplasty. This is a prospective study of 60 patients who underwent myringoplasty and were then followed up for 6 months from the date of operation. Patients with dry perforation, with good cochlear reserve, intact and mobile ossicular chain, functioning Eustachian tube were selected randomly for the operation. Video Otoendoscopy of all cases with storz 0 degree endoscope were done. All images were recorded on the computer [DELL VOSTRO 3400]. Using ‘Image J’ [version 1.35j] geometrical package, the area of perforation (P) and the entire area of the tympanic membrane (T) were calculated. Then, the percentage area of the perforation [P/T × 100 %] for each ear was obtained. Site of perforation also documented. Success rate for pin-point and small perforations was 100 %, for medium size 80 %, and for large & subtotal perforations 69.2 and 42.9 % respectively. We regard size of the perforation as a major factor that influences success of Myringoplasty. Site of perforation failed to be a statistically significant influencing factor in this study.     

Steroid resistant nephrotic syndrome: role of histopathology

This study was conducted to (1) see the histopathological distribution of different subtypes in steroid resistant nephrotic syndrome (SRNS) and (2) compare the clinical, biochemical parameters and outcome between Minimal Change Disease (MCD) with non-MCD subtypes in response to immunosuppressive therapy. A retrospective analysis was done of data on all biopsy proven children with idiopathic SRNS (no response to 4 weeks of standard prednisone therapy (60 mg/m(2)/day)) referred to our institute over last 12 years. They were treated with one of the following medications: oral or intravenous cyclophosphamide, cyclosporine or combination of dexamethasone and azathioprine. A comparison was done of the demographic clinical and biochemical features different histopathologies. We studied 136 children with SRNS (100 M, 36 F). They accounted for 15.1%(136/900) of all children with idiopathic nephrotic syndrome. Focal segmental glomerulosclerosis (FSGS) was the commonest 80/136 (59%), followed by MCD (17.6%). Children with non-MCD had a significantly greater prevalence of microhematuria as compared to MCD. The other baseline clinical and biochemical features including the glomerular filtration rate (GFR) were similar. After a mean follow up of 46 (8-148) months, a significantly greater children with non-MCD 65/112) continued to be proteinuric as compared to the MCD (3/24) (p=0.0001). FSGS was the commonest cause of SRNS in our patient population. Children with SRNS secondary to MCD are more likely to achieve remission as compared to non-MCD subtypes and have a better long-term prognosis. Hence kidney biopsy is of significant prognostic value in SRNS.     

Tandem Plasmapheresis and Hemodialysis

Abstract: Many patients requiring plasmapheresis (PE) have renal failure and also need hemodialysis. If done separately almost 6–7 h is required. Hence, we decided to perform the procedures simultaneously in those patients requiring both PE and hemodialysis. The plasmafilter was inserted into the extracorporeal circuit after the hemodialyzer. A total of 8 such sessions of tandem PE and hemodialysis were performed in 2 patients. This is called tandem PE/hemodialysis. The total procedure was completed in the same time as is required for routine hemodialysis. The total amount of priming fluid is also less when PE and hemodialysis are performed separately. Thus, it is economically beneficial to the hospital and also convenient to the patient. Apart from transient episodes of hypotension, which were corrected by saline infusion, no other complications were noted.     

Intracellular Delivery System for Antibody–Peptide Drug Conjugates

Antibodies armed with biologic drugs could greatly expand the therapeutic potential of antibody–drug conjugates for cancer therapy, broadening their application to disease targets currently limited by intracellular delivery barriers. Additional selectivity and new therapeutic approaches could be realized with intracellular protein drugs that more specifically target dysregulated pathways in hematologic cancers and other malignancies. A multifunctional polymeric delivery system for enhanced cytosolic delivery of protein drugs has been developed that incorporates endosomal-releasing activity, antibody targeting, and a biocompatible long-chain ethylene glycol component for optimized safety, pharmacokinetics, and tumor biodistribution. The pH-responsive polymeric micelle carrier, with an internalizing anti-CD22 monoclonal targeting antibody, effectively delivered a proapoptotic Bcl-2 interacting mediator (BIM) peptide drug that suppressed tumor growth for the duration of treatment and prolonged survival in a xenograft mouse model of human B-cell lymphoma. Antitumor drug activity was correlated with a mechanistic induction of the Bcl-2 pathway biomarker cleaved caspase-3 and a marked decrease in the Ki-67 proliferation biomarker. Broadening the intracellular target space by more effective delivery of protein/peptide drugs could expand the repertoire of antibody–drug conjugates to currently undruggable disease-specific targets and permit tailored drug strategies to stratified subpopulations and personalized medicines.