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Biomedical subjects

D Garfinkel

Publications and source records attributed to D Garfinkel.

At least 19 recordsLinked to original sources
PubMed2000

Melatonin for treatment of sundowning in elderly persons with dementia - a preliminary study.

This pilot study investigated the impact of melatonin administration as a clinical intervention for improving sleep and alleviating sundowning in 11 elderly nursing home residents who suffer from dementia. Melatonin is a hormone produced and secreted by the pineal gland in response to darkness, which plays a major role in the induction and regulation of sleep. Melatonin production decreases with age. Age-related sleep disorders are frequently associated with disruption of circadian cycle rhythms, and sometimes with 'sundowning'. Sundowning refers to the manifestation of agitation and/or confusion in the evening hours. Agitation has been linked to sleep disorders. Analysis revealed a significant decrease in agitated behaviors in all three shifts, and a significant decrease in daytime sleepiness. There was a nonsignificant decrease in latency (time to fall asleep) during the evening shift and no significant changes were reported in night-time sleep ratings. The results of this study are important, because finding ways of decreasing sundowning in elderly persons may improve their well being, alleviate the burden of the caregivers, and even enable caregiving in a less restrictive environment.

Journal Article↗
PubMed1999

Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach.

BACKGROUND: Benzodiazepines are the most frequently used drug for the treatment of insomnia. Prolonged use of benzodiazepine therapy is not recommended. However, many patients, particularly older patients, have difficulties discontinuing therapy. Melatonin, a hormone that is produced at night by the pineal gland, promotes normal sleep in humans and augments sleep induction by benzodiazepine therapy. OBJECTIVE: To assess whether the administration of melatonin could facilitate the discontinuation of benzodiazepine therapy in patients with insomnia. METHODS: Thirty-four subjects receiving benzodiazepine therapy were enrolled in the 2-period study. In period 1, patients received (double-blinded) melatonin (2 mg in a controlled-release formulation) or a placebo nightly for 6 weeks. They were encouraged to reduce their benzodiazepine dosage 50% during week 2, 75% during weeks 3 and 4, and to discontinue benzodiazepine therapy completely during weeks 5 and 6. In period 2, melatonin was administered (single-blinded) for 6 weeks to all subjects and attempts to discontinue benzodiazepine therapy were resumed. Benzodiazepine consumption and subjective sleep-quality scores were reported daily by all patients. All subjects were then allowed to continue melatonin therapy and follow-up reassessments were performed 6 months later. RESULTS: By the end of period 1, 14 of 18 subjects who had received melatonin therapy, but only 4 of 16 in the placebo group, discontinued benzodiazepine therapy (P = .006). Sleep-quality scores were significantly higher in the melatonin therapy group (P = .04). Six additional subjects in the placebo group discontinued benzodiazepine therapy when given melatonin in period 2. The 6-month follow-up assessments revealed that of the 24 patients who discontinued benzodiazepine and received melatonin therapy, 19 maintained good sleep quality. CONCLUSION: Controlled-release melatonin may effectively facilitate discontinuation of benzodiazepine therapy while maintaining good sleep quality.

Adult↗
PubMed1995

Improvement of sleep quality in elderly people by controlled-release melatonin.

Melatonin, produced by the pineal gland at night, has a role in regulation of the sleep-wake cycle. Among elderly people, even those who are healthy, the frequency of sleep disorders is high and there is an association with impairment of melatonin production. We investigated the effect of a controlled-release formulation of melatonin on sleep quality in 12 elderly subjects (aged 76 [SD 8] years) who were receiving various medications for chronic illnesses and who complained of insomnia. In all 12 subjects the peak excretion of the main melatonin metabolite 6-sulphatoxymelatonin during the night was lower than normal and/or delayed in comparison with non-insomniac elderly people. In a randomised, double-blind, crossover study the subjects were treated for 3 weeks with 2 mg per night of controlled-release melatonin and for 3 weeks with placebo, with a week's washout period. Sleep quality was objectively monitored by wrist actigraphy. Sleep efficiency was significantly greater after melatonin than after placebo (83 [SE 4] vs 75 [3]%, p < 0.001) and wake time after sleep onset was significantly shorter (49 [14] vs 73 [13] min, p < 0.001). Sleep latency decreased, but not significantly (19 [5] vs 33 [7] min, p = 0.088). Total sleep time was not affected. The only adverse effects reported were two cases of pruritus, one during melatonin and one during placebo treatment; both resolved spontaneously. Melatonin deficiency may have an important role in the high frequency of insomnia among elderly people. Controlled-release melatonin replacement therapy effectively improves sleep quality in this population.

Aged↗
PubMed1995

A prospective randomized comparison of an attached silver-impregnated cuff to prevent central venous catheter-associated infection.

The VitaCuff catheter, a specialized central venous catheter (CVC) with an attached silver-impregnated cuff, is designed to permit percutaneous placement and prolonged venous access. A prospective randomized study was undertaken comparing the VitaCuff with standard triple lumen catheters to determine if the VitaCuff reduces infection during extended use. All consenting patients underwent percutaneous placement of subclavian lines. By study design, control and VitaCuff catheters could remain in site for up to 7 and 14 days, respectively. Cultures were obtained from the preinsertion skin site, and upon removal, from the skin, hubs, infusates, CVC tip, and cuff. Statistical methods included chi 2, the Student t test, and the log-rank test on Kaplan-Meier estimates. Of 133 patients completing this study, 64 patients (48.1%) underwent VitaCuff placement and 69 patients (51.8%) served as controls. In 124 patients (93.2%), the indication for catheter placement was for perioperative care. Overall, 67 patients (50.4%) required central venous access > 7 days, necessitating > or = 1 additional line in 29 patients (21.8%). The incidence of pneumothorax per patient from the initial central line insertion was 4/104 (3.85%), significantly lower than the 4/29 (13.8%) incidence during secondary catheter placement (P = 0.046). Culture results upon catheter removal demonstrated a reduction in colonization of skin sites and hubs for the VitaCuff patients, but not for catheter tips or infusates. Regardless of the type of catheter used, colonization was dependent upon duration of insertion. The incidence of catheter-related sepsis was 6.8%, and did not differ significantly between the study groups. Multiple CVC insertions increase the incidence of pneumothorax. Because VitaCuff catheters permit extended access up to 14 days without increasing the incidence of sepsis, we recommend their use in patients who require prolonged CVC access.

Catheterization, Central Venous↗
PubMed1994

Preeclampsia and antioxidant nutrients: decreased plasma levels of reduced ascorbic acid, alpha-tocopherol, and beta-carotene in women with preeclampsia.

OBJECTIVE: Our purpose was to investigate the plasma levels of three potent antioxidant nutrients in women with preeclampsia. STUDY DESIGN: Fasting venous blood samples were collected from 30 women with preeclampsia and from 44 women with uncomplicated pregnancies. The criteria for recruitment included age 15 to 35 years, gestational age 28 to 42 weeks, singleton pregnancy, intact membranes, absence of labor contractions, and absence of any other medical complication concurrent with preeclampsia. Reduced ascorbic acid, alpha-tocopherol, and beta-carotene levels were assayed with high-pressure liquid chromatography. RESULTS: Plasma levels of reduced ascorbic acid were significantly decreased in patients with mild and severe preeclampsia (p < 0.01). Plasma alpha-tocopherol and beta-carotene levels were significantly decreased only in severe preeclampsia compared with controls (p < 0.05 and p < 0.05, respectively). CONCLUSION: In patients with preeclampsia antioxidant nutrients may be utilized to a greater extent to counteract free radical-mediated cell disturbances, resulting in a reduction in antioxidant plasma levels. Water-soluble antioxidant nutrients may initially be consumed, followed by lipid-soluble antioxidants.

Adolescent↗
PubMed1994

The cadmium toxicity hypothesis of aging: a possible explanation for the zinc deficiency hypothesis of aging.

Although cadmium and zinc have similar chemical properties, they affect living organisms diversely: while zinc is an essential element for growth, development and functioning of all living cells, cadmium is a highly toxic material. Cadmium has an extremely long biological half-life and may be considered a cumulative toxin. It has been shown to have sterilizing, teratogenic and carcinogenic effects and most of these effects could be reduced or even prevented by zinc administration. An increase in cadmium concentration with age has been proven in various species and in different tissues and these facts led some investigators to the assumption that cadmium accumulation might play an important role in senescence. Zinc essentiality and the lack of a reliable index of intracellular zinc status, formed the rationale for the zinc deficiency hypothesis of aging. This hypothesis suggests a gradual time related zinc deficiency occurring in each living cell, making zinc less available for its metalloenzymes. The sum of all deleterious effects resulting from the distorted function of different zinc enzymes, is later manifested as aging processes. When cadmium concentration increases, zinc concentration in various tissues decreases. Cadmium may inhibit zinc activities at many stages, interfering with zinc absorption, distribution to different tissues and transport into cells or into several intracellular structures. Therefore, it is reasonable to assume that a slowly developing cadmium toxicity may result in a gradual time related zinc deficiency.

Aging↗
PubMed1993

Platinum chemotherapy during pregnancy for serous cystadenocarcinoma of the ovary.

Ovarian carcinoma in pregnancy remains a rare event. Although concern regarding the gestation complicates therapy, platinum drug-based combination chemotherapy is often deemed warranted in such cases. We report the antepartum use of cisplatin, followed by carboplatin, for an ovarian serous cystadenocarcinoma. During this treatment, serial sonographic assessment of fetal morphometric parameters and biophysical profiles with fetal heart rate monitoring were performed to document fetal well being. Platinum-DNA adducts were measured in maternal blood, placenta, fetal amniotic cells, and cord blood. This report represents an attempt to define platinum drug transfer in utero and fetal growth and development during therapy and to document the first use of carboplatin in pregnancy.

Adult↗
PubMed1991

A computer model of pancreatic islet glycolysis.

We have modeled an experiment with perifused pancreatic islet cells using our BIOSSIM language. The experiment and the resulting model are concerned with glucose uptake and glycolysis by the beta-cells of pancreatic islets. Although glycolysis appears to be involved in insulin release, we do not have enough information to represent insulin release in detail. The rapid entry of glucose into the beta-cell is promoted by a carrier having a very high tissue capacity. Phosphorylation of glucose by the low affinity enzyme glucokinase appears to be limiting for glycolysis. The effects of several hexose diphosphate activators of phosphofructokinase are modeled. Model behavior is described. The kinetic parameters of the enzyme submodels are given. Because of the difficulties of preparing large amounts of experimental material, information on pancreatic islet metabolism is limited. This model is a plausible explanation of the experimental results. Recent work on the genetically engineered glucose transporter and glucokinase is discussed.

Animals↗
PubMed1989

An artificial-intelligence technique for qualitatively deriving enzyme kinetic mechanisms from initial-velocity measurements and its application to hexokinase.

We have developed a computer method based on artificial-intelligence techniques for qualitatively analysing steady-state initial-velocity enzyme kinetic data. We have applied our system to experiments on hexokinase from a variety of sources: yeast, ascites and muscle. Our system accepts qualitative stylized descriptions of experimental data, infers constraints from the observed data behaviour and then compares the experimentally inferred constraints with corresponding theoretical model-based constraints. It is desirable to have large data sets which include the results of a variety of experiments. Human intervention is needed to interpret non-kinetic information, differences in conditions, etc. Different strategies were used by the several experimenters whose data was studied to formulate mechanisms for their enzyme preparations, including different methods (product inhibitors or alternate substrates), different experimental protocols (monitoring enzyme activity differently), or different experimental conditions (temperature, pH or ionic strength). The different ordered and rapid-equilibrium mechanisms proposed by these experimenters were generally consistent with their data. On comparing the constraints derived from the several experimental data sets, they are found to be in much less disagreement than the mechanisms published, and some of the disagreement can be ascribed to different experimental conditions (especially ionic strength).

Adenosine Triphosphate↗
PubMed1989

Constraint matching as a means of designing biochemical experiments in multi-enzyme systems.

A method of qualitative analysis by constraint matching, where expectations derived from theory or from data bases are systematically compared against experimental findings, is described. This was originally developed as an artificial intelligence technique to analyze enzyme kinetic mechanism determinations. It is shown to have been used (without computer involvement) in designing experiments involving a few enzymes, and is suggested as a useful experimental design tool. The experiments in question validate the behavior of insulinoma extracts as models for pancreatic islet glycolysis, which conform to the expectations from the relevant enzyme literature. Possible generalization to other areas of biological research is suggested.

Enzymes↗
PubMed1988

Theory formation in postulating enzyme kinetic mechanisms: reasoning with constraints.

This paper reports on a prototype system for modeling and analyzing the expert reasoning involved in postulating enzyme kinetic mechanisms. It involves data-driven, theory-driven, and analogical components of reasoning within a generate-and-test cycle. Its central component is a set of domain-specific "filters" for matching experimentally and theoretically derived constraints. The input to the system consists of an abstracted qualitative description of an experiment and prior knowledge reported in the literature. Its output shows how the results match those expected for a set of postulated reaction mechanism models and also provides a trace of which features do or do not match each of the candidate topological models. Results, constraints, and models are all analyzed and compared to those from other, similar experiments. We deduced rules for interpreting the qualitative features of enzyme kinetic experiments from natural language descriptions in the literature and verified that the rules were correct by predicting the results for typical mechanisms. We obtained the correct behavior for all 37 states of a complex enzyme mechanism involving three substrates and three products. We tested our system on data from several published reports dealing with the enzyme hexokinase and obtained detailed listings of the differences in conclusions and interpretation reported in several journal articles. This system, which provides qualitative representations of enzyme kinetic results, should facilitate further experimentation on theory formation in enzyme kinetics and lead to more efficient experimental designs.

Artificial Intelligence↗
PubMed1988

Pancreatic islet discrimination of hexose anomers. I. Steady-state computer simulation.

Pancreatic islets detect glucose level by phosphorylating it and converting the glycolytic rate to a signal to secrete insulin. Insulin secretion is greater from the alpha- than from the beta-anomer when the D-glucose level is below 22 mM. D-mannose behaves similarly but at nearly twofold higher concentrations. Two explanations have been proposed: 1) glucokinase, which has the same anomeric preference, is the principal hexose phosphorylating enzyme and limits glycolytic rate. 2) Phosphofructokinase limits glycolysis and hexokinase is the principal enzyme phosphorylating hexose; hexosediphosphate activators of phosphofructokinase are more readily synthesized from alpha-anomers of hexose phosphates. We have simulated both alternatives with a detailed anomerically specific model of the hexose-metabolizing glycolytic enzymes. The pathway preference for alpha-anomer of both hexoses was adequately reproduced with anomerically active limiting glucokinase. The other mechanism did not reproduce the observed pathway preference.

Animals↗
PubMed1988

Pancreatic islet discrimination of hexose anomers. II. Transient computer simulation.

We have previously modeled pancreatic islet glycolysis under idealized steady-state conditions where the input is a pure hexose anomer and there is no mutarotation and reproduced the known preference for the alpha-anomers of glucose and mannose as substrates. This model is here extended to simulate real experiments, where the hexoses mutarotate and measurements may be taken over time. The behavior of our model system agrees with available experimental data. The hexose diphosphate activators of phosphofructokinase, whose effect was seen as not important in the preceding steady-state analysis, are found here to have a modest (approximately 10-15%) effect on its flux. The previous conclusion that the anomeric preference of the glycolytic pathway follows from that of glucokinase continues to hold in the real experimental situation.

Animals↗
PubMed1988

Magnesium and regulation of carbohydrate metabolism at the molecular level.

Enzymatic reactions involving the transfer of high-energy phosphate require a divalent metal ion as a participant. This is normally Mg2+ in biological situations, as its level within the cell is greater than other divalent metal ions. Although available methods for determining free cellular Mg2+ have thus far given divergent results, there is a growing body of evidence that its concentration is relatively low, approximately 0.5 mM. This low level permits control of important parts of carbohydrate metabolism, especially glycolysis, by Mg2+. The role of Mg2+ in regulating the phosphoryl-transfer enzymes of this pathway is described. Also described briefly is a series of computer models of this metabolism in heart and pancreatic islets. These models indicate considerable changes in Mg2+ level, and consequent control, especially when there are sharp changes in the glycolytic rate.

Carbohydrate Metabolism↗