Burden of illness among patients with severe aplastic anemia who have had insufficient response to immunosuppressive therapy: a multicenter retrospective chart review study

Annals of Hematology - This study assessed treatment patterns and healthcare resource utilization (HRU) of patients with severe aplastic anemia (SAA) with insufficient response to immunosuppressive...     

Molecular analysis of neuronal physiology by gene transfer into neurons with herpes simplex virus vectors.

A genetic analysis of mammalian neuronal physiology might now be possible due to the development of defective herpes simplex virus vectors, which allow gene transfer directly into mature neurons, in culture or in the adult brain. Genetically altered proteins that play critical roles in neuronal physiology, including those responsible for the generation of action potentials, synthesis and release of neurotransmitters, and signal transduction enzymes, can now be stably expressed in neurons. The effect of such altered proteins on neuronal physiology can therefore be examined, using the tools of modern neuroscience. Genetic manipulation is biochemically specific and stable, and can be targeted both to a particular cell type and to a particular subregion of the cell to yield insights into the molecular basis for specific brain functions.     

A quantitative method of analyzing the interaction of slightly selective radioligands with multiple receptor subtypes

Subclasses of receptors exist for most neurotransmitters. Frequently, two subtypes of receptors coexist in the same tissue and, in some cases, they mediate the same physiological response. In tissues with two classes of binding sites for a given hormone, an estimate of the proportion of each class of binding sites is obtained by inhibiting the binding of a single concentration of a radioligand with a selective unlabeled ligand. Accurate estimates of the density of each class of receptors will only be obtained, however, if the radioligand is entirely nonselective. Selectivity of just 2- to 3-fold can markedly influence the results of subtype analysis. The conclusion that a radioligand is nonselective is usually based on the results of a saturation binding curve. If Scatchard analysis of such data results in a linear plot, then it is concluded that the radioligand is nonselective. However, Scatchard analysis cannot distinguish between a radioligand that is nonselective and one that is slightly selective. The use of a slightly selective radioligand can lead to errors of 50% or more, depending on the concentration of the radioligand relative to the Kd values of the two classes of sites. A new analytical method has been developed that can be used to quantitate 2- to 3-fold differences in the affinity of two distinct classes of binding sites for a radioligand. This new approach requires that a series of inhibition experiments with a selective unlabeled ligand be performed in the presence of increasing concentrations of the radioligand. Analysis of the resulting inhibition curves, utilizing the mathematical modeling program MLAB on the PROPHET system, yields accurate estimates of the density of each class of receptor as well as the affinity of each receptor for the labeled and unlabeled ligands. This approach was used to determine whether 125I-iodopindolol shows selectivity for beta 1- or beta 2-adrenergic receptors. A series of inhibition curves was generated with the unlabeled ligands ICI 89,406 (beta 1-selective) and ICI 118,551 (beta 2-selective), using membranes prepared from C6 glioma cells. These cells contain both beta 1- and beta 2-adrenergic receptors. 125I-Iodopindolol was determined to be 3-fold selective for beta 2-adrenergic receptors. Since the sensitivity of this approach is superior to that of Scatchard analysis, it is likely that other radioligands, previously thought to be nonselective, will be shown to be selective when analyzed by this method.     

Bone mineral status in paraplegic patients who do or do not perform standing

Bone mineral density (BMD) was assessed by dual-photon X-ray absorptiometry at the lumbar spine (L3, L4), the proximal femur and the femoral shaft, and by single-photon absorptiometry at the forearm in 53 patients with complete traumatic paraplegia of at least 1 year's duration and in age- and sex-matched healthy controls. The patients did (n=38) or did not (n=15) regularly perform passive weightbearing standing with the aid of a standing device. Compared with the controls, the BMD of paraplegic patients was preserved in the lumbar spine and was markedly decreased in the proximal femur (33%) and the femoral shaft (25%). When considering all patients performing standing, they had a better-preserved BMD at the femoral shaft (p=0.009), but not at the proximal femur, than patients not performing standing. BMD at the lumbar spine (L3,L4) was marginally higher in the standing group (significant only for L3;p=0.040). A subgroup of patients performing standing with use of long leg braces had a significantly higher BMD at the proximal femur than patients using a standing frame or a standing wheelchair (p=0.030). The present results suggest that passive mechanical loading can have a beneficial effect on the preservation of bone mass in osteoporosis found in paraplegics.     

Cholelithiasis: a serious complication after total gastrectomy

To establish the incidence of cholelithiasis after total gastrectomy, patients operated on between 1979 and 1985 were reviewed. The study group consisted of 30 patients, all free of gallstones at the time of their gastrectomy. The median age of the patients was 56 years, the average follow-up 40 months. Cholelithiasis developed in 47 per cent of patients (14/30) and always within 2 years of total gastrectomy. The incidence of cholelithiasis was not related significantly to the sex or age of the patients. Morbidity from cholelithiasis was not negligible. Three of the fourteen patients presenting with gallstones required medical treatment in hospital and later came to cholecystectomy because of specific biliary symptoms. Cholelithiasis appears to be a significant complication after total gastrectomy. It may be related to the vagotomy which is performed at the time of gastrectomy.     

Development of novel dental cements. I. Formulation of aluminoborate glasses

Aluminoborate glasses were formulated as potential novel glass-ionomer cement components, and their reactivity with a polyalkenoic acid was assessed by means of working and setting time measurements. Of the 20 prepared formulations, some containing fluoride, eight were found to have acceptable manipulative characteristics, and three of these formed hard set materials.     

Validation and application of polymer gel dosimetry for the dose verification of an intensity-modulated arc therapy (IMAT) treatment

Polymer gel dosimetry was used to assess an intensity-modulated arc therapy (IMAT) treatment for whole abdominopelvic radiotherapy. Prior to the actual dosimetry experiment, a uniformity study on an unirradiated anthropomorphic phantom was carried out. A correction was performed to minimize deviations in the R2 maps due to radiofrequency non-uniformities. In addition, compensation strategies were implemented to limit R2 deviations caused by temperature drift during scanning. Inter- and intra-slice R2 deviations in the phantom were thereby significantly reduced. This was verified in an investigative study where the same phantom was irradiated with two rectangular superimposed beams: structural deviations between gel measurements and computational results remained below 3% outside high dose gradient regions; the spatial shift in those regions was within 2.5 mm. When comparing gel measurements with computational results for the IMAT treatment, dose deviations were noted in the liver and right kidney, but the dose-volume constraints were met. Root-mean-square differences between both dose distributions were within 5% with spatial deviations not more than 2.5 mm. Dose fluctuations due to gantry angle discretization in the dose computation algorithm were particularly noticeable in the low-dose region.     

The value of radiographic film for the characterization of intensity-modulated beams

In this paper the performance of radiographic film (KODAK X-Omat V) for analysing intensity-modulated (IM) beams in a plane at reference depth (5 cm for 6 MV, 10 cm for 18 MV) was investigated. The field size dependence of the film response was studied for small and medium field sizes. The dose rate dependence of the response and possible effects of fractionating the dose were assessed. In the end, profiles were measured for two clinically delivered IM beams, and the results were compared with diamond detector data. We found that the response of the radiographic film increases with field size, but for field sizes up to 15 x 15 cm the deviations remain within 3% for measurements with the films in a plane at reference depth. We found that the response of the films decreases with decreasing dose rate, and that the extent of this effect differs from film batch to film batch. For clinical IM beams the effect can amount to about 9% at the location of shielded organs at risk. Also, fractionating the dose reduces the net optical density, but this effect is normally small when assessing IM beams. In low-dose regions low-energy photons have an important contribution, resulting in a higher response at these positions. This may counteract the dose rate dependence of the response. In the high-dose regions of the two IM beams that were studied, the relative dose measurements with film are within 1% of those obtained with a diamond detector, when the results of three films are averaged. In shielded organs at risk the deviations can mount to about 3%, depending on the film batch. In conclusion, radiographic film is a suitable detector for characterizing IM beams in a plane at reference depth.     

Resolution of Diabetes Following Vertical Gastroplasty in Morbidly Obese Patients

Case reports are presented on three patients treated for morbid obesity by vertical gastroplasty. Prior to surgery the patients had diabetes which required insulin, up to 200 units per day, or oral hypoglycaemics for its control. Six months after surgery the diabetes had been resolved in all three patients, and they were no longer dependent on medication. Subjective reports from the patients suggests that their quality of life improved significantly.