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Biomedical subjects

D Packard

Publications and source records attributed to D Packard.

9 recordsLinked to original sources
PubMed1999

Efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for prevention of stroke.

OBJECTIVE: To determine if 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in preventing fatal and nonfatal strokes in patients at increased risk of coronary artery disease. DESIGN: Meta-analysis of randomized controlled trials. Clinical trials were identified by a computerized search of MEDLINE (1983 to June 1996), by an assessment of the bibliographies of published studies, meta-analyses and reviews, and by contacting pharmaceutical companies that manufacture statins. Trials were included in the analysis if their patients were randomly allocated to a statin or placebo group, and reported data on stroke events. Thirteen of 28 clinical trials were selected for review. Data were extracted for details of study design, patient characteristics, interventions, duration of therapy, cholesterol measurements, and the number of fatal and nonfatal stroke events in each arm of therapy. Missing data on stroke events were obtained by contacting the investigators of the clinical trials. MAIN RESULTS: Among 19,921 randomized patients, the rate of total stroke in the placebo group was 2.38% (90% nonfatal and 10% fatal). In contrast, patients who received statins had a 1.67% stroke rate. Using an exact stratified analysis, the pooled odds ratio (OR) for total stroke was 0.70 (95% confidence interval [CI] 0.57, 0.86; p =.0005). The pooled OR for nonfatal stroke was 0.64 (95% CI 0.51, 0.79; p =.00001), and the pooled OR for fatal stroke was 1.25 (95% CI 0.71, 2.24; p =.4973). In separate analyses, reductions in total and nonfatal stroke risk were found to be significant only for trials of secondary coronary disease prevention. Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the relative risk for any stroke outcome. CONCLUSIONS: The available evidence clearly shows that HMG-CoA reductase inhibitors reduce the morbidity associated with strokes in patients at increased risk of cardiac events. Data from 13 placebo-controlled trials suggest that on average one stroke is prevented for every 143 patients treated with statins over a 4-year period.

Aged↗
PubMed1994

Comparative biochemical characteristics of the cat and rabbit urinary bladder.

The cat and the rabbit are two of the most popular models for the study of lower urinary bladder function. The cat has been used extensively for in vivo studies of spinal and supra-spinal micturition reflexes. In contrast, the rabbit has been used extensively for the in vitro study of bladder function. Although the cat and rabbit bladders are approximately the same mass, the cat bladder can generate approximately 6 times the intravesical pressure than the rabbit bladder at the same volume (in vitro response to field stimulation). In order to determine if the increased pressure generation is related to increased cellular energetics, we compared the intracellular concentrations of ATP and creatine phosphate (CP), and the enzyme activities of three enzymes which have important functions in cellular energetics: creatine kinase, citrate synthase, and malic dehydrogenase between the cat and rabbit urinary bladder. The results can be summarized as follows: (1) The bladder weight of the cat and rabbit are similar. (2) The isolated cat bladder can generate approximately 6 times the intravesical pressure of the isolated rabbit bladder. (3) The ATP and CP concentrations of the rabbit are significantly greater than the concentrations in the cat bladder. (4) The hydroxyproline concentration is significantly greater in the cat than the rabbit. (5) The maximum activities of creatine kinase, citrate synthase, and malic dehydrogenase are significantly lower in the cat than the rabbit. In general, it is clear that the ability of the cat to generate high intravesical pressures is not correlated with increased tissue high energy phosphate concentrations, or high enzymatic activities of three specific cytosolic or mitochondrial enzymes.

Adenosine Triphosphate↗
PubMed1993

Effect of partial outlet obstruction on choline acetyltransferase activity in the rat and rabbit.

Partial outlet obstruction of the rabbit bladder induces a rapid and significant increase in bladder mass. This increase in mass is associated with a variety of specific contractile dysfunctions, characterized by a marked decrease in the response to field stimulation (acting through the release of neurogenic transmitters). There is histological evidence indicating that the decrease in the contractile response of isolated strips of rabbit urinary bladder to field stimulation is associated with a degeneration of synaptic membranes within the bladder detrusor (neuropathy). In the current experiments, the effect of partial outlet obstruction in rabbit and rat urinary bladders on choline acetyltransferase activity (ChAT) were determined and correlated with both the level of bladder hypertrophy (increase in mass) and the contractile response to field stimulation. The results can be summarized as follows: In the rabbit, partial outlet obstruction induced a rapid 5-fold increase in bladder mass over the 7 day period of study. This increase in mass was associated with a decrease in the contractile response of isolated strips of bladder body and base to field stimulation and a decrease in ChAT activity. Interestingly, the rabbit bladder base showed a significantly higher ChAT activity than the bladder body, although the contractile response to muscarinic stimulation was significantly greater in the bladder body than in the base. In the rat, partial outlet obstruction induced a mild 2-fold increase in bladder mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effect of outlet obstruction on pyruvate metabolism of the rabbit urinary bladder.

Bladder function is dependent upon cellular metabolism of substrates and the adequate generation of high-energy phosphate compounds. Partial outlet obstruction induces a marked decrease in bladder function which is associated with a significant decrease in the oxidative metabolism of glucose. The current investigation was designed to determine whether the time course of the decrease in mitochondrial oxidation in the hypertrophied urinary bladder is similar to the time course of the contractile dysfunction observed. In these studies we determined: 1) the rate of 14C-pyruvate metabolism to 14CO2 in control and obstructed tissue (1, 3, 5 and 7 days), and 2) the mitochondrial enzymatic activities of malate dehydrogenase and citrate synthase. The results can be summarized as follows: 1) The rate of pyruvate metabolism decreases by over 50% within one day following partial outlet obstruction, and remains at this level for the seven day period of study. 2) Kinetic analysis demonstrates that the change in enzymatic activity is related to a decrease in Vmax; the Kd for pyruvate is similar for control and after all time periods of obstruction. 3) The enzymatic activity of malate dehydrogenase and citrate synthase is reduced by over 50% within one day following partial obstruction, and remains at this level throughout the 7 day study period. These metabolic results correlate in time and duration with the decreased ability of the bladder to empty following partial outlet obstruction.

Animals↗
PubMed1992

Effect of ryanodine on mitochondrial respiration.

Ryanodine is a pharmacological agent that stimulates calcium leakage into the cytoplasm resulting in an increase in tension. In skeletal muscle, ryanodine acts primarily on the sarcoplasmic reticulum whereas in smooth muscle, the sites of action are less clear. Visually, the increase in tension is slow and the time course can be mimicked by mitochondrial poisoning and the resultant leak of mitochondrial calcium into the cytoplasm. Although it has been reported that ryanodine has no effect on calcium flow into or from mitochondria, the effect of ryanodine on mitochondrial oxidative function was not studied. In the current investigation direct measurements of the effect of ryanodine on mitochondrial oxygen utilization were made. The results demonstrate that ryanodine, even at high concentrations, has no effect (stimulatory or inhibitory) on mitochondrial oxidation.

Animals↗
PubMed1979

Sensory extinction and sensory reinforcement principles for programming multiple adaptive behavior change.

The role of sensory reinforcement was examined in programming multiple treatment gains in self-stimulation and spontaneous play for developmentally disabled children. Two phases were planned. First, we attempted to identify reinforcers maintaining self-stimulation. Sensory Extinction procedures were implemented in which auditory, proprioceptive, or visual sensory consequences of self-stimulatory behavior were systematically removed and reintroduced in a reversal design. When self-stimulation was decreased or eliminated as a result of removing one of these sensory consequences, the functional sensory consequence was designated as a child's preferred sensory reinforcer. In Phase 2, we assessed whether children would play selectively with toys producing the preferred kind of sensory stimulation. The results showed the following. (1) Self-stimulatory behavior was found to be maintained by sensory reinforcement. When the sensory reinforcer was removed, self-stimulation extinguished. (2) The sensory reinforcers identified for self-stimulatory behavior also served as reinforcers for new, appropriate toy play. (3) The multiple treatment gains observed appeared to be relatively durable in the absence of external reinforcers for play or restraints on self-stimulation. These results illustrate one instance in which multiple behavior change may be programmed in a predictable, lawful fashion by using "natural communities of sensory reinforcement."

Autistic Disorder↗