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Biomedical subjects

D Stone

Publications and source records attributed to D Stone.

At least 109 records · Page 6Linked to original sources
PubMed1991

Comparison of a hand-held nebulizer with a metered dose inhaler-spacer combination in acute obstructive pulmonary disease.

This study compared the effect of "standard" dose metaproterenol delivered by hand-held nebulizer (HHN) with two puffs of metaproterenol delivered by a metered dose inhaler (MDI) via a spacer (InspirEase) (MDI-spacer). Seventeen patients with an acute exacerbation of obstructive pulmonary disease were studied. Each patient received both MDI-spacer and HHN. Alternate patients were randomized to either MDI-spacer or HHN as initial treatment. Each subject was tested four different times: before and 30 minutes after the initial aerosol delivery technique, and before and 30 minutes after the alternate aerosol delivery technique. Testing consisted of spirometry, lung auscultation, and measurement of vital signs. The interval between treatments for all subjects was 2.96 +/- 0.27 hours (mean +/- SEM) and was not different for subjects who received therapy via MDI-spacer first or HHN first. The patient population studied demonstrated severe airways obstruction (baseline FEV1 33.3 percent predicted +/- 4.9 percent). There was a statistically significant improvement in FVC and FEV1 after metaproterenol delivered by HHN, but not after MDI-spacer. Metaproterenol treatment with HHN resulted in a greater improvement in FEV1 (p less than .05) than MDI-spacer when the data were reported as absolute improvement (0.19 +/- 0.05 L for HHN) vs (0.06 +/- 0.03 L for MDI-spacer) or reported as percent change (23.2 +/- 6.6 percent for HHN) vs (9.5 +/- 3.4 percent for MDI-spacer). Asthmatic patients exhibited a significantly greater (p less than 0.05) improvement in FEV1 after HHN (23.4 +/- 4.7 percent change) than after MDI-spacer (6.6 +/- 4.5 percent change). Patients with chronic obstructive pulmonary disease (COPD) exhibited a greater improvement in FVC (p less than 0.05) after HHN (25.2 +/- 6.7 percent change) than after MDI-spacer (5.8 +/- 4.7 percent change). We conclude that the "standard" dosage of metaproterenol delivered by HHN results in greater spirometric improvement in patients with acute obstructive pulmonary disease than the conventional dosage of metaproterenol delivered by MDI-spacer. It is likely that this reflects the fact that the recommended dose of metaproterenol delivered by MDI is too low and should be increased.

Acute Disease↗
PubMed1991

Mitochondria, oxygen and reperfusion damage.

Reperfusion of the ischaemic or hypoxic heart elicits a number of oxygen dependent processes such as cell lysis and Ca2+ uptake. It is known that the energisation of mitochondria, which requires oxygen, plays a key role in these processes and that the organelle actively sequesters Ca2+ under these circumstances. In this brief review we discuss how oxidants derived from mitochondrial electron transport may perturb mitochondrial calcium handling on reoxygenation of the hypoxic myocardium. In addition we show that the immunosuppressive agent cyclosporin has little or no effect on the oxygen dependent increase in total cell Ca2+ which occurs when hypoxic myocytes are reoxygenated. This result suggests that the Ca2+ dependent mitochondrial pore, which is known to function under conditions of oxidative stress, does not play a major role in the perturbation of Ca2+ homeostasis which occurs on reoxygenation of hypoxic hearts.

Adenosine Triphosphate↗
PubMed1990

Conservative management of cervical pregnancy with subsequent fertility.

The reported incidence of cervical pregnancies with subsequent fertility is extremely low. We report a case managed conservatively that allowed for future fertility, and ultimately the delivery of a viable infant at term. The conservative management and a review of the literature are discussed.

Adult↗
PubMed1990

Electrocardiographic manifestations of combined hypercalcemia and hypermagnesemia.

Near drowning in the Dead Sea is a potentially lethal accident; the swallowing of the salty water causes acute combined hypercalcemia and hypermagnesemia, and this, rather than aspiration, is considered to be the main pathogenetic fator. The authors reviewed the electrocardiographic data of 37 patients who nearly drowned in the Dead Sea. Common findings in the acute phase included P wave changes, tendency for prolongation of P-R interval, prolongation of QRS complex, infra-His conduction disturbances, tendency for broadening and inversion of T wave, and the appearance of a prominent U wave. Three patients had potentially lethal ventricular tachyarrhythmias. The QaTc interval (beginning of QRS complex to apex of T wave, corrected for heart rate), the expected QaTc calculated from calcium blood level (QaTce), and their difference (DQaTc), were measured or calculated. The QaTc was found within normal limits and did not change during recovery from the Dead Sea water poisoning. The DQaTc correlated significantly with serum magnesium level (p less than 0.001). This correlation signifies that hypermagnesemia normalizes the QaTc interval, which is usually shortened by isolated hypercalcemia. Combined hypercalcemia and hypermagnesemia can be caused by swallowing excessively salty water. The potential cardiac complications require strict monitoring and electrocardiographic follow up study.

Arrhythmias, Cardiac↗
PubMed1990

Interaction of a liver-specific factor with an enhancer 4.8 kilobases upstream of the phosphoenolpyruvate carboxykinase gene.

We have previously identified a series of five DNase-I hypersensitive (HS) sites within and around the rat phosphoenolpyruvate carboxykinase (PEPCK) gene. The far upstream region has now been sequenced, and the tissue-specific HS site has been mapped more precisely at 4,800 base pairs upstream of the transcription start site of the PEPCK gene. DNA fragments that include the HS site were cloned upstream of various promoters to test whether these regions modulate transcription of the chloramphenicol acetyltransferase reporter gene. Chloramphenicol acetyltransferase activity was enhanced when the DNA fragment encompassing the upstream HS site was linked to various lengths of the PEPCK promoter or to the heterologous simian virus 40 promoter. This upstream region in conjunction with the proximal promoter, which may contain a tissue-specific element, conferred maximum activation in H4IIE hepatoma cells, which express the endogenous PEPCK gene. When these experiments were performed in XC cells, in which the gene is not expressed, transcriptional activation by the upstream element was still significant. Evidence of a specific protein-DNA interaction, using DNA mobility shift and DNase I footprinting assays, was obtained only when using H4IIE cell nuclear extracts. Competition assay showed that the interacting factor may be similar or identical to the liver-specific factor HNF3. We suggest that this protein factor binds to DNA within the HS site and interacts with the proximal promoter region to control tissue-specific high-level expression of the PEPCK gene.

Animals↗
PubMed1989

Activity of bleomycin in iron- and copper-deficient cells.

Three models were used to examine the requirement of bleomycin (Blm) for iron (Fe) to carry out its antitumor or cytotoxic activity. Mice were made iron deficient by dietary means. Animals with depressed iron stores in liver and low plasma and ascites fluid iron supported Ehrlich tumor growth as well as mice maintained on a control diet. Bleomycin was equally effective against this tumor in iron-deficient mice as it was against the tumor in iron-sufficient controls. Likewise, nutrient copper deficiency did not change the efficacy of the drug. Ehrlich cells in culture were treated with a non-growth inhibiting concentration of the chelating agent, 1,10-phenanthroline before or during their exposure to bleomycin. Again, the treated cells were as sensitive to drug as controls, despite the fact that this ligand reduces cellular iron and zinc and can extract iron from Fe(II)Blm. Lastly, it was demonstrated that iron-depleted Euglena gracilis cells growing at reduced rates were as sensitive to growth inhibition by bleomycin as control cells.

Animals↗
PubMed1989

Hypoxia-reoxygenation induced increase in cellular Ca2+ in myocytes and perfused hearts: the role of mitochondria.

Reoxygenation of isolated rat cardiac myocytes following a period of hypoxia and substrate deprivation resulted in a 1.5-2-fold increase in the total Ca2+ content which could be inhibited by 1 microM antimycin A or ruthenium red (50% inhibition at 2.5 microM). This increase in Ca2+ content was not accompanied by any release of creatine kinase into the medium. Treatment of reoxygenated cells with digitonin also resulted in an antimycin A-sensitive increase in Ca2+ but this was inhibited by a lower concentration of ruthenium red (50% inhibition at 0.25 microM) and was associated with a substantial release of creatine kinase from the cells. It is concluded that the reoxygenation-stimulated increase in Ca2+ is dependent on functioning mitochondria and does not occur as a result of physical damage to the sarcolemma. In a parallel series of experiments, the effects of antimycin A and ruthenium red on the reoxygenation-induced increase in Ca2+ and release of cytosolic contents in the perfused heart (the oxygen paradox) were also investigated. As was observed with the isolated myocytes, each of the compounds significantly reduced the magnitude of the Ca2+ increase that occurred on reoxygenation: the compounds also reduced the extent of release of cell contents in the perfused heart. The implications of these results for the series of events occurring on reoxygenation of the hypoxic myocardium are discussed.

Animals↗
PubMed1989

Epidemiologic characteristics of scabies in the Israel Defense Force.

Scabies is not a notifiable disease in most countries. As a result the data on its epidemiologic characteristics are limited. In the Israel Defense Force, compulsory reporting of individual cases has been required for years, and in this study the epidemiology of the disease is examined for the years 1968-1988. A moderate epidemic occurred between 1969 and 1973, and was followed by a return to the previous low incidence. In 1982 a massive outbreak began, and peaked from 1985-1986. From 1987 to 1988, the incidence of infestation has markedly declined. A seasonal pattern of morbidity was evident during epidemic periods only; maximum incidence occurred during the winter months. These data are compared with those described in other countries and provide a more complete picture of the epidemiology of scabies based on individually reported cases.

Adolescent↗
PubMed1989

Switching of Candida albicans during successive episodes of recurrent vaginitis.

Strain relatedness and switching were monitored in Candida albicans strains isolated from different body locations through three episodes of recurrent vulvovaginal candidiasis separated by two treatment-latency periods in a single patient. Strain relatedness was assessed by comparing Southern blot hybridization patterns with the relatively immobile mid-repeat sequence Ca3. The following conclusions are demonstrated. (i) Three different strains of C. albicans colonized the mouth, the area under the breasts, and the vulvovaginal, anal, and rectal regions, respectively, at the time of the first infection. (ii) The same strain of C. albicans was responsible for the three vaginal infections. (iii) Switching of colony phenotype occurred with each new vaginal infection. (iv) Enrichment of drug-resistant switch phenotypes (assessed in vitro) was unlikely the basis for the changes in the switch phenotypes of the strain found in the vulvovaginal, anal, and rectal areas after treatment of the first infection with clotrimazole. (v) The same strain of C. albicans was responsible for the recurrent increases in mouth colonization and was distinct from the recurrent vaginal strain. The results of this case study demonstrate the need for further detailed analyses of full-body mycofloras, strain relatedness, switching repertoires, and changes in drug susceptibility during successive episodes of recurrent vulvovaginal candidiasis.

Antifungal Agents↗
PubMed1989

The glutathione status of perfused rat hearts subjected to hypoxia and reoxygenation: the oxygen paradox.

Langendorff perfused rat hearts were subjected to 30 min hypoxia followed by 20 min reoxygenation and the levels of the oxidised and reduced forms of glutathione measured. No change in the concentration of oxidised glutathione was detected in reoxygenated hearts when compared to normoxic controls. In contrast hearts exposed to oxidative stress in the form of H2O2 showed elevated levels of both oxidised glutathione (GSSG) and the glutathione-protein mixed disulphide. These results suggest that if oxidants do contribute to cell damage on reoxygenation of the hypoxic myocardium then their action is local and not through overwhelming of the cells antioxidant defences.

Animals↗
PubMed1989

Oxygen and reperfusion damage: an overview.

The ischaemic myocardium shows a number of distinct oxygen dependent responses to reperfusion. In the case of myocardial stunning and reperfusion arrhythmias there appears to be a beneficial effect of scavenging radicals in the extracellular space. This result is supported by the finding that free radicals can be detected extracellularly after reperfusion. The source of these oxidants and site of action is as yet unclear. In contrast hypoxic myocytes shown an oxygen dependent Ca2+ uptake on reoxygenation which is not affected by externally applied antioxidants. This Ca2+ uptake may in turn lead to the cell lysis characteristic of the oxygen paradox in the perfused heart. As yet there is no compelling evidence to suggest that this aspect of reperfusion damage is due to oxidative stress. It appears more likely that mitochondrial electron transport and ion movement play a central role. In the open chested dog model of ischaemia reperfusion, in which the volume of infarcted tissue is measured, considerable evidence suggests that oxidants derived from activated neutrophils contribute to cell death. This is not however the sole mechanism for cell damage in this model since an inhibitor of mitochondrial Ca2+ uptake, ruthenium red, can improve recovery after reperfusion. We conclude that a number of mechanisms may contribute to the observed oxygen dependent dysfunctions which occur on reperfusion of ischaemic tissue.

Animals↗
PubMed1988

A comparative study of the cardiovascular and biochemical actions of the imidazo [4,5b] pyridine sulmazole and an imidazo [4,5c] pyridine analogue, BW A746C.

1. BW A746C is a chemical analogue of the imidazo [4,5b] pyridine, sulmazole (AR-L115 BS). Like sulmazole, BW A746C possesses positive inotropic and vasodilator activity in vivo. 2. In anaesthetized guinea-pigs, dogs and primates, a bolus i.v. injection of BW A746C, (0.001-1.0 mg kg-1) caused a significant, dose-related increase in ventricular dP/dt, and reduction in diastolic blood pressure, with small increases in heart rate. In these species, a significantly higher dose of BW A746C was required to lower blood pressure by 30% from basal, than was needed to raise ventricular dP/dt by 50% over basal. 3. In anaesthetized guinea-pigs and dogs, bolus i.v. injections of sulmazole (0.1-10.0 mg kg-1) caused similar effects to those observed with BW A746C. In these species, however, there was no significant difference between the dose of sulmazole required to lower blood pressure by 30% from basal and that required to raise ventricular dP/dt by 50%. 4. In conscious dogs, i.v. infusion of BW A746C (to a total dose of 0.3 mg kg-1) caused a significant increase in ventricular dP/dt, but no significant change in either diastolic blood pressure or heart rate. 5. In cell-free biochemical assays, there were no clear differences between the observed activities of BW A746C and sulmazole. Both compounds are cyclic nucleotide phosphodiesterase inhibitors with similar potencies and selectivities for the Type III enzyme (IC50 BW A746C = 3.0 +/- 0.5 X 10(-5) M, sulmazole 5.0 +/- 1.9 X 10(-5) M). The compounds had little or no effects on sarcolemmal Na+/K+-ATPase, Ca2+ ATPase or Na+/Ca2+ exchange, and sulmazole, but not BW A746C, had a small, stimulatory effect on myofibrillar ATPase. 6. In anaesthetized guinea-pigs and dogs, BW A746C was significantly more potent as a positive inotrope than sulmazole. In contrast with sulmazole, BW A746C produced its inotropic effects at significantly lower doses than those required to reduce diastolic blood pressure. This was also apparent from the results obtained in the anaesthetised primates and the conscious dogs. It was therefore concluded that the inotropic/vasodilator profile of BW A746C favours its positive inotrope activity. This profile cannot be explained on the basis of any biochemical differences from sulmazole.

Animals↗
PubMed1988

Reciprocal regulation of antral gastrin and somatostatin gene expression by omeprazole-induced achlorhydria.

Gastric acid exerts a feedback inhibition on the secretion of gastrin from antral G cells. This study examines whether gastrin gene expression is also regulated by changes in gastric pH. Achlorhydria was induced in rats by the gastric H+/K+ ATPase inhibitor, omeprazole (100 mumol/kg). This resulted in fourfold increases in both serum gastrin (within 2 h) and gastrin mRNA levels (after 24 h). Antral somatostatin D cells probably act as chemoreceptors for gastric acid to mediate a paracrine inhibition on gastrin secretion from adjacent G cells. Omeprazole-induced achlorhydria reduced D-cell activity as shown by a threefold decrease in antral somatostatin mRNA levels that began after 24 h. Exogenous administration of the somatostatin analogue SMS 201-995 (10 micrograms/kg) prevented both the hypergastrinemia and the increase in gastrin mRNA levels caused by omeprazole-induced achlorhydria. Exogenous somatostatin, however, did not influence the decrease in antral somatostatin mRNA levels seen with achlorhydria. These data, therefore, support the hypothesis that antral D cells act as chemoreceptors for changes in gastric pH, and modulates somatostatin secretion and synthesis to mediate a paracrine inhibition on gastrin gene expression in adjacent G cells.

Achlorhydria↗