Differential dependency of cutaneous mechanoreceptors on neurotrophins, trk receptors, and P75 LNGFR

The impact of null mutations of the genes for the NGF family of neurotrophins and their receptors was examined among the wide variety of medium to large caliber myelinated mechanoreceptors which have a highly specific predictable organization in the mystacial pad of mice. Immunofluorescence with anti-protein gene product 9.5, anti-200-kDa neurofilament protein (RT97), and anti-calcitonin gene-related product was used to label innervation in mystacial pads from mice with homozygous null mutations for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), the three tyrosine kinase receptors (trkA, trkB, trkC), and the low-affinity nerve growth factor receptor p75. Specimens were sacrificed at birth and at 1, 2, and 4 weeks for each type of mutation as well as at 11 weeks and 1 year for p75 and trkC mutations, respectively. Our results demonstrate several major concepts about the role of neurotrophins in the development of cutaneous mechanoreceptors that are supplied by medium to large caliber myelinated afferents. First, each of the high-affinity tyrosine kinase receptors, trkA, trkB, and trkC, as well as the low-affinity p75 receptor has an impact on at least one type of mechanoreceptor. Second, consistent with the various affinities for particular trk receptors, the elimination of NGF, BDNF, and NT-3 has an impact comparable to or more complex than the absence of their most specific high-affinity receptors: trkA, trkB, and trkC, respectively. These complexities include potential NT-3 signaling through trkA and trkB to support some neuronal survival. Third, most types of afferents are dependent on a different combination of neurotrophins and receptors for their survival: reticular and transverse lanceolate afferents are dependent upon NT-3, NGF, and trkA; Ruffini afferents upon BDNF and trkB; longitudinal lanceolate afferents upon NGF, trkA, BDNF, and trkB; and Merkel afferents on NGF, trkA, NT-3, trkC, and p75. NT-4 has no obvious detrimental impact on the mechanoreceptor development in the presence of BDNF. Fourth, NT-4 and BDNF signaling through trkB may suppress Merkel innervation and NT-3 signaling through trkC may suppress Ruffini innervation. Finally, regardless of the neurotrophin/receptor dependency for afferent survival and neurite outgrowth, NT-3 has an impact on the formation of all the sensory endings. In the context of these findings, indications of competitive and suppressive interactions that appear to regulate the balance of innervation density among the various sets of innervation were evident.     

Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18

PURPOSE: To identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: Multivariable Cox models were constructed to evaluate the strength and statistical significance of baseline risk factors for development of high-risk PDR and of SVLV. RESULTS: The baseline characteristics identified as risk factors for high-risk PDR were increased severity of retinopathy, decreased visual acuity (or increased extent of macular edema), higher glycosylated hemoglobin, history of diabetic neuropathy, lower hematocrit, elevated triglycerides, lower serum albumin, and persons with mild to moderate nonproliferative retinopathy, younger age (or type 1 diabetes). The predominant risk factor for development of SVLV was the prior development of high-risk PDR. The only other clearly significant factor was decreased visual acuity at baseline. In the eyes that developed SVLV before high-risk proliferative retinopathy was observed, baseline risk factors were decreased visual acuity (or increased extent of macular edema), older age (or type 2 diabetes), and female gender. CONCLUSIONS: These analyses supported the view that the retinopathy-inhibiting effect of better glycemic control extends across all ages, both diabetes types, and all stages of retinopathy up to and including the severe nonproliferative and early proliferative stages and the possibility that reducing elevated blood lipids and treating anemia slow the progression of retinopathy.     

Thrombolytic therapy for acute myocardial infarction

Numerous factors must be considered when determining the formulary status of thrombolytic agents for the treatment of acute myocardial infarction. Defined treatment options, predicted outcomes, and the economic consequences of this disorder continue to evolve from clinical trials. Pharmacists have a major role in delivering patient care, with responsibility for evaluating, procuring, and monitoring thrombolytic agents and drug therapy in general. By participating in the development and implementation of treatment guidelines, evaluating economic and therapeutic outcomes, providing timely optimal drug therapy, and educating health care providers and the public, they contribute significantly to the health care team.     

Postoperative complications of elective surgeries in dogs and cats determined by examining electronic and paper medical records

Postoperative complications (POC) that developed in dogs and cats that underwent elective ovariohysterectomy, castration, and declaw at a veterinary teaching hospital were determined by examining the computerized abstracts of the medical records and by examining a random sample of the paper medical records. When the computerized abstracts were examined, POC were found to have occurred in 62 (6.1%) of 1,016 dogs. One dog died and 6 others developed major complications. Postoperative complications were found to have occurred in 38 (2.6%) of 1,459 cats. Two cats died and 1 was euthanatized. Four other cats developed major complications. Complete paper medical records for 218 dogs and cats were examined. When the paper medical records were examined, the proportions of dogs and cats with POC were 19.4% and 12.2%, respectively. These proportions were 4 to 7 times higher than when the computerized abstracts were the data source. Results of this study indicate that the frequency of clinically relevant POC of elective surgeries in dogs and cats is substantial. Examination of the computerized abstracts of medical records at this hospital allowed us to rapidly identify cases that could be included in the study but the frequency of POC would be significantly underestimated if paper records were not also assessed.     

Dynamic three-dimensional display of common congenital cardiac defects from reconstruction of two-dimensional echocardiographic images

PURPOSE: To investigate the effects of acetone or water based Gluma primers on bonding efficacy when applied to acid-etched wet, dry or rewetted dentin. MATERIALS AND METHODS: Shear bond strength (SBS, 24 hours) was measured on human dentin etched with 20% phosphoric acid gel and rinsed with water in the wet (blot dried), the conventional (2 seconds air blast), the dry (10 seconds air drying), and the rewetted stage (10 seconds air drying, remoistening and blot drying). The priming solution was either the original water based or an acetone based experimental Gluma primer. Cavity sealing performance and depth of resin impregnation were determined by solvent and by technique along the margins of 4.5 mm wide cylindrical dentin cavities with 90 degree cavosurface angle. RESULTS: The SBSs of the wet technique groups were approximately 18 MPa, irrespective of the primer solvent. Conventional drying gave an SBS almost as high (16.5 MPa). Rewetting was highly effective with acetone as the primer solvent. The dry techniques resulted in moderate (water) and poor (acetone) bond strengths. The cavity margins of acetone based primer treated specimens were consistently gap free with the wet technique. The other seven groups showed between two and six gaps in each group of six specimens. The resin impregnated layer (RIL) thicknesses were 12.5 microns approximately in the wet groups, and thus identical with the total depth of demineralization resulting from the 30-second etching. The alternative techniques showed significantly thinner RILs particularly in the dry groups (7.5 microns).     

Iliac artery stenoses after percutaneous transluminal angioplasty: follow-up with duplex ultrasonography

PURPOSE: To assess iliac artery stenosis before and up to 1 year after percutaneous transluminal angioplasty (PTA) with duplex ultrasound (DUS) to determine the incidence of residual and recurrent stenoses and correlate these findings to clinical outcome. PATIENTS AND METHODS: Sixty-one patients with 70 iliac artery segments treated with PTA were examined. The peak systolic velocity (PSV) ratio (PSV ratio = PSV in stenosis divided by PSV proximal or distal to stenosis) was determined by DUS before PTA and 1 day, 3 months and 1 year after PTA. Three categories of results were identified by using PSV ratios at the site of the treated stenosis 1 day and 1 year after PTA (good result, residual stenosis, and recurrent stenosis). The DUS-determined anatomic result was correlated with the clinical outcome at 1 year. Clinical outcome was classified according to Society for Vascular Surgery/International Society for Cardiovascular Surgery (SVS/ISCVS) criteria. RESULTS: Good results with DUS (PSV ratio 1 day and 1 year after PTA > or = to 2.5) were found in 45 of 70 segments (64.3%), residual stenoses (PSV ratio > or .5 1 day after PTA) in 15 of 70 segments (21.4%), and recurrent stenosis (PSV ratio 1 day after PTA < 2.5 and 1 year after PTA > or = 2.5) in 10 of 70 segments (14.3%). PSV ratios of residual stenoses decreased significantly between 1 day and 1 year after PTA because some residual stenoses improved hemodynamically in time. Clinical results were significantly better in patients with a good result compared with other patients. However, the clinical outcome of patients with residual stenoses was not significantly different from the patients with good DUS results. CONCLUSION: Some residual stenoses improved sonographically after PTA. Clinical results at 1 year are highly variable within different groups. Clinical outcome of patients with residual stenoses did not differ from patients with good DUS results, whereas clinical outcome in patients with recurrent stenoses was worse than in the other groups.     

Statistical framework for ultrasonic spectral parameter imaging

This study examines the statistics of ultrasonic spectral parameter images that are being used to evaluate tissue microstructure in several organs. The parameters are derived from sliding-window spectrum analysis of radiofrequency echo signals. Calibrated spectra are expressed in dB and analyzed with linear regression procedures to compute spectral slope, intercept and midband fit, which is directly related to integrated backscatter. Local values of each parameter are quantitatively depicted in gray-scale cross-sectional images to determine tissue type, response to therapy and physical scatterer properties. In this report, we treat the statistics of each type of parameter image for statistically homogeneous scatterers. Probability density functions are derived for each parameter, and theoretical results are compared with corresponding histograms clinically measured in homogeneous tissue segments in the liver and prostate. Excellent agreement was found between theoretical density functions and data histograms for homogeneous tissue segments. Departures from theory are observed in heterogeneous tissue segments. The results demonstrate how the statistics of each spectral parameter and integrated backscatter are related to system and analysis parameters. These results are now being used to guide the design of system and analysis parameters, to improve assays of tissue heterogeneity and to evaluate the precision of estimating features associated with effective scatterer sizes and concentrations.     

Neoadjuvant chemotherapy and radiotherapy for inoperable head and neck cancer: the LSU-Shreveport experience

A retrospective review of 8 years of treatment in 2 hospitals in Shreveport showed that neoadjuvant chemotherapy with radiotherapy was performed in 39 patients with inoperable, locally advanced head and neck cancer. Twenty-two individuals treated by definitive radiotherapy alone served as historical controls. The cumulative survival rate at 4 years was 34% in patients managed by neoadjuvant chemotherapy with radiotherapy and 7% in patients treated by radiotherapy only. With the exception of greater acute toxicity seen in patients receiving neoadjuvant chemotherapy with radiotherapy, differences in locoregional failure, distant metastasis, and late complication rates were not observed between the patient groups.     

Newly developed initial-flow cell filtrometer and the comparison with viscometry and ektacytometry on erythrocyte deformability

According to Hanss's initial-flow rate method, F. Liao designed a new cell filtrometer in the early 1990s. The parameters, cell initial transit time (Tc) and membrane clogging rate (CR), can be determined by a single measurement with timing accuracy of 1 ms. The new cell filtrometer has two valuable features: a button-pushing operation to control electromagnetic valves; and an autocirculation of fluid in the cell filtrometer resulting in the same volume of leading fluid. A series of comparisons of the new filtrometry with viscometry or ektacytometry shows that the instrument seems to be more sensitive in detecting subpopulations of glutaraldehyde-hardened cells and the shift of deformability for all the cells. The reproducibility of the filtrometer for different membranes made in China and the USA is reasonable (CV < 5% for Tc). Preliminary application of the filtrometer indicates that it might be useful for trial study and routine clinical application.