Telemedicine: What have we learned?

As the health care industry is facing many challenges and is undergoing extensive change, telemedicine is in the position to address these challenges and be an important part of health care's development. Telemedicine has been used for approximately a half century, in which researchers have explored the different technologies utilized, clinical outcomes, cost benefits, perceptions, and adoption challenges of its use. This paper reviews and summarizes these findings and presents possible future research endeavors. Examining what is known about telemedicine can aid in the development of innovative, sustainable and beneficial health technologies that could positively impact health care delivery and outcomes.

Characterization of the role of the "MT-loop": an eight-amino acid insertion specific to progelatinase A (MMP2) activating membrane-type matrix metalloproteinases.

Progelatinase A (proGLA) activation is thought to be initiated almost exclusively by the type I transmembrane members of the membrane type matrix metalloproteinase family (MT-MMP): MT1, -2, -3, and -5-MMP (MMP14, -15, -16, and -24). One difference between these enzymes and the other MMP family members is the insertion of eight amino acids between strands betaII and III in the catalytic domain. In MT1-MMP, the best characterized of these enzymes to date, these residues consist of (163)PYAYIREG(170). To investigate the role of this region of MT1-MMP on its catalytic activities, we have made a variety of mutations and deletions in both soluble and membrane-bound forms of the enzyme. Characterization of the activity of the soluble forms toward peptides and fibrinogen revealed that neither mutation nor deletion of residues 163-170 significantly impaired catalytic function, suggesting these residues have little influence on conformation of the active site cleft. Equally none of the mutants showed significant differences in K(I)(app) for the N-terminal inhibitory domain of TIMP2, again indicating that mutation or deletion of resides 163-170 has no major effect on the overall topology of the active site of MT1-MMP. However, characterization of the kinetics of activation of proGLA with and without its gelatin binding region by the mutants generated have shown that efficient activation of proGLA is, at least in part, through an interaction with residues 163-170 of MT1-MMP. The expression, localization, and processing from the 63- to the 60/45-kDa forms of wild-type and key mutant forms of MT1-MMP were also examined by transient transfection in Chinese hamster ovary cells, but no differences were observed. Processing and activation of proGLA was also examined in transiently transfected cells. All the mutants examined were able process proGLA but, as found with the soluble forms, were kinetically impaired when compared with wild-type MT1-MMP.

Effects of high-molecular-weight cryoprotectants on platelets and the coagulation system.

The objective of this study is to examine the effects of the most widely used high-molecular-weight cryoprotectants on the coagulation system. Dextran, hydryoxyethyl starch (HES), polyvinyl pyrrolidone (PVP), polyethylene glycol (PEG), and albumin were added at different concentrations in the range between 0.01-1% (w/v) to solvent/detergent-treated plasma. Using a STA/STA Compact coagulation analyzer the following clotting tests were performed: prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Factor V, and Factor VIII percentage of activity. PVP and PEG caused a significant increase in APTT, a decrease in Factor VIII percentage of activity, and a slight decrease in TT, while PT and Factor V percentage of activity remained unchanged. Dextran, HES, and albumin did not effect the clotting tests. The effect of high-molecular-weight cryoprotectants on platelets was assessed by platelet-induced clot retraction (PICR) and aggregation with thrombin and agglutination with ristocetin. Platelet aggregation and agglutination were unaffected by all cryoprotectants tested; however, PICR was significantly reduced in the presence of PVP or PEG. Possible mechanisms by which PVP and PEG interfere with the coagulation system are discussed. We also raise issues concerning the development of one-step blood cryopreservation techniques which do not require cryoprotectant removal prior to transfusion.

Mycoflora of Stone Fruit Mummies in California Orchards.

Stone fruit mummies infected by Monilinia fructicola were periodically collected in winter from trees and from the ground in eight orchards in 1995-96 and from five orchards in 1996-97. Mycoflora were determined by spreading mummy washings and plating inner tissues onto petri dishes containing acidified potato dextrose agar, then counting colonies of individual fungi after incubation at 23°C for 4 days. Twenty genera, representing 29 fungal species, were isolated from both mummy washings and inner tissues. Aspergillus japonicus, A. terreus, and species of Harknesia, Paecilomyces, and Trichoderma are the first recorded from species of Prunus in the United States, and Aureobasidium pullulans and Epicoccum purpurascens are the first reported for California. The principal mycoflora recovered from mummy washings were species of non-filamentous yeasts (32.1%), Penicillium (28.8%), Cladosporium (11.4%), and Mucor (10.8%). Major mycoflora of mummy inner tissues were species of Penicillium (23.7%), Mucor (19.6%), Cladosporium (17.3%), and Rhizopus (11.1%). The relative recoveries of individual fungi from mummy inner tissues differed with location, Prunus species, and sampling position (tree or ground), and changed as the season progressed. The relative recovery of M. fructicola from mummy inner tissues was negatively correlated with Botrytis (R = -0.53, P = 0.0052), Penicillium (R = -0.58, P = 0.0681), and Rhizopus (R = -0.50, P = 0.0696). These results could help obtain naturally occurring antagonists and maximize their use in biocontrol systems aimed at reducing primary inoculum for blossom blight of stone fruits in California orchards.

Role of the S1' subsite glutamine 215 in activity and specificity of stromelysin-3 by site-directed mutagenesis.

The influence of Gln215 in stromelysin-3 (MMP-11), a residue located in the S1' subsite, was determined by producing three single mutants of this position. As compared to wild-type stromelysin-3, the kinetic parameters K(M) and k(cat) for the degradation of the fluorogenic substrate Dns-Pro-Leu-Ala-Leu-Trp-Ala-Arg-NH(2) (Dns-Leu) by these mutants indicated that the Gln/Leu substitution led to a 4-fold decrease in catalytic efficiency, whereas the mutations Gln/Tyr and Gln/Arg increased this parameter by a factor 10. The cleavage of alpha1-protease inhibitor (alpha1-PI), a natural substrate of stromelysin-3, by these mutants was also determined. Their relative activities for the degradation of alpha1-PI correspond to those observed with the synthetic substrate Dns-Leu. The catalytic efficiency of wild-type stromelysin-3 and its mutants to cleave the P1' analogue of Dns-Leu, containing the unusual amino acid Cys(OMeBn) (Dns-Cys(OMeBn)), was also determined. The values of the specificity factor, calculated as the ratio (k(cat)/K(M))Dns-Cys(OMeBn))/(k(cat)/K(M))Dns-Leu, were observed to vary from 26 for the wild-type stromelysin-3 to 120 for the Gln/Leu mutant and 25 for the Gln/Arg mutant. The Gln/Tyr mutant did not cleave the substrate when its P1' position is substituted by the unusual amino acid Cys(OMeBn). Altogether these observations established that both the catalytic activity and the specificity of stromelysin-3 are dependent on the nature of the residue in position 215. Finally, the cleavage efficiency of the Dns substrates by three representative matrixins, namely, MMP-14 (215 = Leu), MMP-1 (215 = Arg), and MMP-7 (215 = Tyr), was determined. Interestingly, the trends observed for these enzymes were similar to those established for the three mutants of stromelysin-3, pointing out the influence of position 215 toward the selectivity in this family of enzymes.

Effects of preinspiratory volume on the nitrogen closing volume test.

The effect of varying the preinspiratory volume (VIair; range: 0-75% vital capacity, VC) on the nitrogen closing volume (CV) test was studied in twelve seated subjects, aged 24-62 years. When VIair was increased from 0 to about 12% VC, the height of phase IV, the amplitude of the cardiogenic oscillations, CV and the slope of phase III increased. The height of phase IV and the amplitude of the cardiogenic oscillations showed a maximum at VIair = 12% VC, although the average CV was about 18% VC. While the height of phase IV and the amplitude of the cardiogenic oscillations decreased when VIair was increased above 12% VC, CV did not change and the slope of phase III increased consistently. These results cannot be explained solely by the regional lung volume model of Sutherland et al. (1968). However, if that model is extended to include the assumption that within a region alveoli behind closed airways may be differently expanded, we predict CV to be underestimated at low VIair, independently of the upper to lower nitrogen concentration difference, in agreement with present findings. This assumption would also explain why the maximal height of phase IV can be obtained at a VIair lower than CV.

Prediction of postoperative hypoxemia in smokers and non-smokers.

Age, weight, spirometric variables, peak expiratory flow and airway closure assessments were correlated to postoperative gas exchange in 40 cholecystectomized subjects grouped according to smoking history. Pao2 was significantly lower in the smoking group both pre- and postoperatively, but the decrease in Pao2 following operation was of the same magnitude irrespective of smoking history. In non-smokers, the preoperative relationship between expiratory reserve volume and closing volume (ERV-CV) showed the highest correlation to postoperative alveolar-arterial oxygen difference P(A-a)o2 (r = -0.88, P less than 0.001) and to the increase of P(A-a)o2 following operation (r = -0.67, P less than 0.001), whereas age was found to be the best preoperative predictor of postoperative gas exchange in smokers.

Effect of inspired volume on airway closure in relation to age.

Closing volume (CV) was measured in 64 healthy subjects aged 18--76 years, in supine position, with a bolus (helium) technique in two ways: following a maximal (CV100) and a submaximal (=50% VC; CV50) inspiration from residual volume. With increasing age CV50 increased less than CV100 according to the equation CV100(%VC)-CV50(%VC)=0.13Xage-0.6(r=0.46, P less than 0.001), e.g. at 70 years of age CV100=32(%VC) and CV50=24(%VC). Therefore, during normal breathing elderly subjects to not presumably close airways at as high a lung volume as predicted from conventional CV-measurements. A strong correlation between CV50 and CV100 was found, CV50(%VC)=0.55XCV100(%VC)+5.3(r=0.90; P less than 0.001), thus allowing a more accurate prediction of CV50 from CV100 than from age. Neither smoking habits nor body position affected the decrease of CV with reduced inspired volume.

Effect of inspired volume on closing volume.

Closing volume (CV) was ?EASURED WITH THE RESIDENT GAS TECHNIQUE IN 12 HEALTHY SEATED SUBJECTS AGE 22-70 YR, AND IN 8 SUBJECTS WITH THE BOLUS TECHNIQUE. Various volumes were inspired (Vi range: 20-100% vital capacity) from residual volume and CV was assessed on the subsequent recording of expired volume versus gas concentration. The results indicate that the resident gas technique may erroneously underestimate CV at reduced Vi in conformity with calculations which predict that during expiration, after a certain reduced VI, the nitrogen concentration is identical in the most basal lung region and at the mouth. CV obtained with the bolus technique decreased linearly with reduced Vi and the effect appeared to be age dependent according to the equation CV50/CV100=0.0078 X age +1.18, where CV50 and CV100 denote the bolus CV corresponding to Vi=50% and 100% of vital capacity. Therefore, in older subjects, during tidal breathing, airways appear to close at substantially lower lung volume than previously considered.