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Biomedical subjects

G Harris

Publications and source records attributed to G Harris.

At least 55 records · Page 3Linked to original sources
PubMed1999

The new telecare: emerging Internet-based models for home healthcare.

Today's prevalent home telecare model is based on POTS or ISDN-mediated interactive video, and largely replicates conventional provider/client interactions. While this "classical model" may be struggling (see Focus Story, p. 27), a new breed of applications is arising which represents quite a different way of doing business. Each takes a low-tech, low-cost approach to leveraging the value of the Internet. Any of these different models has the potential of opening up a whole new way of providing care and improving self-care. So ... in contrast to the sober tone of this month's feature report, it's a pleasure to be able to report here on some very innovative new Internet-based approaches that promise to leapfrog over many of the institutional, bureaucratic, and technological barriers facing classical home telecare.

California↗
PubMed1998

Rustmicin, a potent antifungal agent, inhibits sphingolipid synthesis at inositol phosphoceramide synthase.

Rustmicin is a 14-membered macrolide previously identified as an inhibitor of plant pathogenic fungi by a mechanism that was not defined. We discovered that rustmicin inhibits inositol phosphoceramide synthase, resulting in the accumulation of ceramide and the loss of all of the complex sphingolipids. Rustmicin has potent fungicidal activity against clinically important human pathogens that is correlated with its sphingolipid inhibition. It is especially potent against Cryptococcus neoformans, where it inhibits growth and sphingolipid synthesis at concentrations <1 ng/ml and inhibits the enzyme with an IC50 of 70 pM. This inhibition of the membrane-bound enzyme is reversible; moreover, rustmicin is nearly equipotent against the solubilized enzyme. Rustmicin was efficacious in a mouse model for cryptococcosis, but it was less active than predicted from its in vitro potency against this pathogen. Stability and drug efflux were identified as two factors limiting rustmicin's activity. In the presence of serum, rustmicin rapidly epimerizes at the C-2 position and is converted to a gamma-lactone, a product that is devoid of activity. Rustmicin was also found to be a remarkably good substrate for the Saccharomyces cerevisiae multidrug efflux pump encoded by PDR5.

Animals↗
PubMed1998

Mechanism of maxi-K channel activation by dehydrosoyasaponin-I.

Dehydrosoyasaponin-I (DHS-I) is a potent activator of high-conductance, calcium-activated potassium (maxi-K) channels. Interaction of DHS-I with maxi-K channels from bovine aortic smooth muscle was studied after incorporating single channels into planar lipid bilayers. Nanomolar amounts of intracellular DHS-I caused the appearance of discrete episodes of high channel open probability interrupted by periods of apparently normal activity. Statistical analysis of these periods revealed two clearly separable gating modes that likely reflect binding and unbinding of DHS-I. Kinetic analysis of durations of DHS-I-modified modes suggested DHS-I activates maxi-K channels through a high-order reaction. Average durations of DHS-I-modified modes increased with DHS-I concentration, and distributions of these mode durations contained two or more exponential components. In addition, dose-dependent increases in channel open probability from low initial values were high order with average Hill slopes of 2.4-2.9 under different conditions, suggesting at least three to four DHS-I molecules bind to maximally activate the channel. Changes in membrane potential over a 60-mV range appeared to have little effect on DHS-I binding. DHS-I modified calcium- and voltage-dependent channel gating. 100 nM DHS-I caused a threefold decrease in concentration of calcium required to half maximally open channels. DHS-I shifted the midpoint voltage for channel opening to more hyperpolarized potentials with a maximum shift of -105 mV. 100 nM DHS-I had a larger effect on voltage-dependent compared with calcium-dependent channel gating, suggesting DHS-I may differentiate these gating mechanisms. A model specifying four identical, noninteracting binding sites, where DHS-I binds to open conformations with 10-20-fold higher affinity than to closed conformations, explained changes in voltage-dependent gating and DHS-I-induced modes. This model of channel activation by DHS-I may provide a framework for understanding protein structures underlying maxi-K channel gating, and may provide a basis for understanding ligand activation of other ion channels.

Animals↗
PubMed1998

National survey of school counselors working with deaf and hard of hearing children. Two decades later.

The first national survey of school counselors for deaf children was conducted by Marie Curtis in 1975. She found that deaf students needed counseling services and that existing services were poor to fair in meeting these students' needs. The purpose of the present study was to follow up on Curtis's study by seeking current information on the demography of school counselors as well as the present roles and skills of counselors working with deaf children. Survey respondents indicated that they spent most of their time providing individual and group counseling. A large majority of respondents said their communication skills with students were adequate or better. The three most frequently identified student problems seen were "problems with peer relations," "difficulty with decision making." and "poor self-esteem." Comparisons between the present study and the Curtis study indicate that counselor competence has improved in the intervening years. Specifically, survey respondents in the present study gave themselves much higher ratings in the areas of communication skills, training, and counseling skills.

Adult↗
PubMed1997

Effect of warfarin on regional left atrial coagulation activity in mitral stenosis.

Increased regional left atrial (LA) coagulation activity has recently been implicated in the pathophysiology of LA thrombus and systemic embolism in mitral stenosis (MS). Anticoagulation with warfarin reduces the risk of such thromboembolism, but the effect of warfarin on LA coagulation activity is unknown. We have addressed this question in MS patients with normal or prolonged clotting times. Peripheral venous and LA coagulation activities were measured in MS patients on long-term oral anticoagulation, who were predisposed to increased LA coagulation activity because of the presence of LA spontaneous echo contrast. Patients ceased warfarin 4 days before percutaneous balloon mitral valvuloplasty, and had either a normal (n = 15) or prolonged (n = 8) International Normalized Ratio (INR) at valvuloplasty. Coagulation activity was assessed during the valvuloplasty procedure, but before valve dilation, by measuring levels of prothrombin fragment 1 + 2 (F1 + 2), a marker of thrombin generation. The LA F1 + 2 level exceeded the peripheral venous level in patients with a normal INR (p <0.001), but these levels were similar in patients with a prolonged INR (p = 0.16). Moreover, the LA (p <0.005) and peripheral venous (p <0.03) F1 + 2 levels, as well as the LA-peripheral venous F1 + 2 difference (p <0.03) were lower in patients with a prolonged INR. These results suggest that anticoagulation with warfarin in MS not only reduces systemic coagulation activity but is associated with a greater reduction in LA coagulation activity. The latter may contribute to the reduced risk of LA thrombus formation that accompanies warfarin therapy in MS.

Aged↗
PubMed1997

Insulin requirements and metabolic control in children with diabetes mellitus attending a summer camp.

The metabolic control of 33 children aged 7-12 (mean 9.8 years), 19M:14F, with diabetes attending a 7-day physically active summer camp was evaluated. Insulin dose was reduced by 20% on arrival at camp, and adjusted daily to maintain preprandial capillary glucose between 4 and 11 mmol l-1 and overnight glucose above 7 mmol l-1. Despite a mean reduction in insulin dose of 33%, hypoglycaemia was common especially in the first few days of camp. This suggests that on day 1 of a physically active camp an empiric reduction of 30% in insulin dose would be more appropriate. However, it is also essential to increase daily carbohydrate intake and New Zealand's national guidelines for the management of diabetes mellitus in summer camps are being rewritten to include this advice. In addition, extra carbohydrate portions must be given simultaneously with insulin dose reduction, especially in physically active camps.

Blood Glucose↗