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Biomedical subjects

G Dodd

Publications and source records attributed to G Dodd.

At least 19 recordsLinked to original sources

Heat stress increases cardiac HSP72i but fails to reduce myocardial infarct size in rabbits 24 hours later.

Recent reports suggest that delayed myocardial protection ("second window of preconditioning") occurs 24 hours after brief ischemic or thermal stress. In order to test this hypothesis, we subjected New Zealand White rabbits to a heating regimen (42 degrees C for 15-20 minutes). Twenty four hours later, the effect of heat stress on infarct size was determined by conducting a 30 minute ischemia/3 hour reperfusion protocol. In a separate group of rabbits, Western blot analysis was used to verify that the heating regimen increased expression of HSP72i. The size of the region at risk was delineated by infusion of Unisperse blue and infarcted myocardium was identified by incubation of left ventricular slices in triphenyl tetrazolium chloride. In contrast to expectations, induction of HSP72i with thermal stress was not effective in limiting infarct size in rabbits 24 hours later, calling into question the concept that heat stress induces delayed or "second window" myocardial protection.

Animals↗

Transjugular intrahepatic portosystemic shunt in the management of variceal bleeding: indications and clinical results.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has proved to be a successful bridge to liver transplantation in the management of variceal bleeding. The safety and ease of this technique has now challenged standard surgical approaches to portal hypertension. To define the role of TIPS, we prospectively studied patients undergoing this procedure for variceal bleeding and/or ascites. METHODS: From September 1991 to September 1992, 45 patients entered a protocol that included assessment of liver chemistries, ammonia levels, coagulation profiles, liver synthetic function by caffeine-antipyrine clearance, ultrasonographic evaluation of hepatic and portal veins, portogram and direct measurement of portal vein pressures, upper endoscopy, computed tomography for liver volume and ascites, and formal neuropsychiatric evaluation. These studies were repeated at 3-month intervals or more frequently if bleeding or complications occurred. RESULTS: Technical success and control of bleeding were achieved in all patients with only three (7%) variceal rebleeds from recurrent portal hypertension. Complete and permanent control of clinical ascites was noted in all patients with this complication. Five of six deaths occurred from sepsis and multiorgan failure in intensive care unit-bound patients with Child class C liver disease. No serial changes were noted in liver chemistries; however, progressive loss of liver volume and prolongation of caffeine-antipyrine clearance was observed in most patients. In addition, hepatic vein stricture or shunt stenosis seen in nine patients (20%) required TIPS revision, whereas the frequent appearance of symptomatic encephalopathy was a main indication for transplantation in 11 of 14 patients. CONCLUSIONS: TIPS successfully controls variceal bleeding and may serve as a novel approach to control of diuretic resistant ascites. The uncertain long-term patency and progressive decline in synthetic function emphasize the importance of initiating proper trials comparing TIPS with other management strategies before indiscriminant use of this technique is seen.

Ascites↗

Erythrocyte fatty acids in multiple sclerosis.

Analysis of the fatty acids in the erythrocyte lipid of multiple sclerosis patients in Italy gave no indication of any difference in composition compared with that of a healthy control group. Supplementation of the diet of another group of similar patients with polyunsaturated fatty acids led to increases in the erythrocyte levels of linoleate and docosahexaenoate, with concomitant falls in oleate and elaidate. Levels of fatty acids such as lignocerate and nervonate that are found predominantly in sphingomyelin were similar in all 3 groups.

Adult↗

Pulmonary hypoplasia testing in clinical obstetrics.

An ultrasound-based diagnostic test for predicting pulmonary hypoplasia antenatally by measurements of fetal chest circumference was applied prospectively to 45 patients at risk for developing this disorder. The outcome for the newborn infant and the autopsy findings were correlated with the antenatal prediction. The results of this test demonstrated a sensitivity and a specificity of 88% and 96%, respectively. The application of this test to clinical practice is recommended.

Amniotic Fluid↗

Clinical utility of multiple-dose administration of prostaglandin E2 gel.

An open-label study was undertaken to assess the clinical impact of multiple doses of intracervical prostaglandin E2 (0.5 mg) gel administered at 6-hour intervals. Fifty women with low Bishop scores requiring induction of labor were recruited. The prestudy mean Bishop score was 2.3 +/- 1.1 and changed significantly with one (p less than 0.001), two (p less than 0.001), and three (p less than 0.002) doses. The mean gestational age of patients receiving three doses was significantly less than that of patients receiving one dose, (38.5 versus 40.1 weeks, p less than 0.005). Prostaglandin E2 gel induced labor in 56% of patients, but 14% required subsequent oxytocin (Syntocinon) augmentation. Cesarean section was performed in 6% of patients. No deleterious fetal, neonatal, or maternal effects occurred.

Adult↗

Doppler ultrasound prediction of fetal outcome in twin pregnancies.

The usefulness of pulsed Doppler ultrasound in predicting twin pregnancies destined for unsatisfactory outcomes was examined in 30 twin pregnancies. Fetal flow velocity waveform analysis (systolic/diastolic ratio and pulsatility index) and quantitative analysis in the descending aorta and umbilical artery demonstrated good sensitivity and specificity when compared with biparietal diameter and abdominal circumference measurements. This technique shows some promise as a useful adjunct in the management of twin pregnancies.

Aorta, Thoracic↗

Successful medical management of neutropenic enterocolitis in adults with acute leukemia.

Seven adults with acute leukemia had a clinical and radiologic diagnosis of neutropenic enterocolitis. Six of the seven patients had granulocyte counts less than 500/microliter. All seven patients responded to intensive medical therapy, including bowel rest, broad spectrum antibiotics, and white blood cell transfusions, and recovered from the neutropenic enterocolitis without surgical intervention. We discuss the clinical spectrum of neutropenic enterocolitis and the favorable results of medical therapy.

Adult↗

Effective oral treatment of severe Paget's disease of bone with APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate); a comparison with combined calcitonin + EHDP (1-hydroxyethylidene-1,1-bisphosphonate).

Ten patients with severe Paget's disease of bone and serum alkaline phosphatase (sAP) greater than 900 IU/l were treated for six months with the oral diphosphonate APD, (3-amino-1-hydroxypropylidene-1, 1-bisphosphonate). By the end of the treatment period there was a reduction in the log mean urine hydroxyproline (uHP) and the log mean sAP of 92% and 87% respectively. In four patients both sAP and uHP fell to within the normal range and remained normal for at least six months after therapy was stopped. Bone scintigraphy showed a fall in 99mTc-MDP uptake in sites of active Paget's disease in all patients and histomorphometry showed no increase in osteoid. Repair of radiological osteolytic lesions was observed in 6/6 patients and progression of tibial osteolytic wedges was arrested in 5/5 patients and reversed in four. This improvement persisted six months after completion of therapy but further wedge progression occurred in one patient whose urine HP remained elevated. There were no serious effects though five patients complained of nausea. The clinical and biochemical responses to APD were equivalent to those observed in the same patients during a previous six month course of combined therapy with human calcitonin (CT) + EHDP except that there was additional biochemical and radiological evidence of bone healing. This study confirms PAD as an effective treatment of severe Paget's disease of bone.

Aged↗

Cervical ripening and labor induction with intracervical triacetin base prostaglandin E2 gel: a placebo-controlled study.

A double-blind, randomized, placebo-controlled study was undertaken to evaluate the efficacy of a single-dose, shelf-stable preparation of prostaglandin E2 gel (PGE2) when used intracervically in patients with low Bishop scores. Two different preparations (0.5 and 0.25 mg) of PGE2 were used and a total of 45 patients were studied. Both preparations of PGE2 demonstrated a statistically significant increase in the spontaneous labor rate as compared with the placebo gel. Bishop scores were altered in all patients not proceeding to labor spontaneously, but the changes were most significant in the low- and high-dose groups. No significant deleterious affects were noted. The efficacy and safety of this new, sterile, and stable preparation makes it suitable for clinical use.

Apgar Score↗

Analysis of discrimination mechanisms in the mammalian olfactory system using a model nose.

Olfaction exhibits both high sensitivity for odours and high discrimination between them. We suggest that to make fine discriminations between complex odorant mixtures containing varying ratios of odorants without the necessity for highly specialized peripheral receptors, the olfactory systems makes use of feature detection using broadly tuned receptor cells organized in a convergent neurone pathway. As a test of this hypothesis we have constructed an electronic nose using semiconductor transducers and incorporating design features suggested by our proposal. We report here that this device can reproducibly discriminate between a wide variety of odours, and its properties show that discrimination in an olfactory system could be achieved without the use of highly specific receptors.

Animals↗

A chemical-modification approach to the olfactory code. Studies with a thiol-specific reagent.

The effects of thiol-specific reagents on the amplitude of the electro-olfactogram (E.O.G.) responses elicited from frog olfactory mucosa by pulses of odorant vapours was studied. The impermeant thiol-specific reagent mersalyl [(3-{[2-(carboxymethoxy)-benzoyl]amino}-2-methoxypropyl)hydroxymercury monosodium salt] brings about a rapid decrease in the E.O.G. signal obtained with the odorant pentyl acetate. The extent of the decrease is proportional to the concentration of the mersalyl applied and the effect of the reagent is partially but incompletely reversed by treatment of the labelled mucosa with dithiothreitol. The sites labelled by mersalyl can be protected by pretreating the mucosa with a dilute solution of the odorant pentyl acetate and leaving the solution in contact with the tissue after the addition of mersalyl. When the protecting odorant is washed out of the tissue, the original E.O.G. amplitude is regained. Pentyl acetate applied to the mucosa protected the E.O.G. response to vapour pulses of the following odorants from the effects of mersalyl: n-butyric acid, n-butyl acetate, phenylacetaldehyde and cineole (1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane). The pentyl acetate applied to the mucosa failed to protect the E.O.G. response to vapour pulses of the following odorants from the effects of mersalyl: butan-1-ol, benzyl acetate, nitrobenzene, beta-ionone and linalyl acetate. The significance of the differential protection effects for the odour-quality-coding mechanism in the olfactory primary neurons is discussed. It is suggested that the olfactory code at this level of the olfactory system may be elucidated by chemical-modification methods.

Acetates↗

The interaction of phospholipid membranes and detergents with glutamate dehydrogenase.

1. The interaction of beef liver glutamate dehydrogenase with cardiolipin from both beef liver mitochondria and beef heart mitochondria, with phosphatidylcholine from both beef liver mitochondria and egg-yolk, and with beef brain phosphatidylserine was investigated by steady-state kinetic methods. 2. the phosphatidylcholine did not inhibit the enzyme under a wide range of conditions. The cardiolipins and phosphatidylserine inhibited the enzyme. The inhibition by these lipids was found to diminish with time if the lipids were prepared and the reaction was studied in either phosphate or Tris buffers, but in zwitterionic buffers these lipid brought about a rapid, reversible inhibition which remained stable with time for at least 150 min. 3. The kinetic type of the inhibition was difficult to determine because of variation between lipid sonicates. Complex mixed types of inhibition were found with cardiolipin, and with phosphatidylserine the inhibition approximated to a non-competitive interaction with Ki(app) values varying between (0.9-6.1) x 10(-6)M. 4. The extent of inhibition decreased with increasing pH and with increasing ionic strength. Basic proteins, such as cytochrome c, show a higher affinity for the anionic membranes and can dissociate the enzyme-lipid complexes. Cosonicates of the cardiolipin and phosphatidylcholine inhibited the enzyme, the extent of inhibition increasing in proportion to the amount of acidic lipid. 5. Sodium dodecylsulphate causes a time-dependent inhibition of the enzyme. The kinetics of this effect and its variation with detergent concentration were studied. 6. The relationship of these observations to the structure and function of the enzyme is discussed. It is suggested that their apparent regulation of the enzyme by oestrogens and other small molecules is due to their binding in vitro at sites on the enzyme designed for binding cardiolipin, when the enzyme is functioning in vivo. The association of the enzyme oligomer in vitro may, for similar reasons, be an artifact.

Animals↗

The interaction of phospholipid membranes and detergents with glutamate dehydrogenase.

1. Both the anionic detergent sodium dodecylsulphate and the cationic detergent cetyltrimethylammonium bromide quenched the protein fluorescence of glutamate dehydrogenase. The anionic compound was more effective and brought about 50% quenching at a detergent concentration of 0.4 mM. The zwitterionic amphiphile, lysolecithin, did not quench the protein fluorescence and neither did the short-chain detergent n-hexylsulphonate, which under the range of concentrations examined (less than 1 mM) does not form micelles. 2. The zwitterionic phospholipid, phosphatidylcholine, did not quench the protein fluorescence but the anionic phospholipids, phosphatidylserine and cardiolipin, induced a reversible quenching of the enzyme fluorescence. These observations confirm the specificity of the phospholipid-enzyme interactions as deduced from the kinetic studies of the preceding paper. The degree of quenching brought about by the phospholipids decreased with increasing ionic strength and increasing pH and could be substantially reduced by basic proteins. An electrostatic contribution to the interaction is inferred from these results. 3. The binding of the anionic phospholipids to the enzyme is manifested in a further enhancement of the fluorescence of a 1-anilinonaphthalene-8-sulphonate-enzyme complex. The presence of substrates and allosteric effectors affect the interaction of the lipids with the enzyme as indicated by the magnitude of this increase in fluorescence. The enhancement of fluorescence of NADH when bound to the enzyme was not affected by the binding of the lipids. 4. The complex formed between the enzyme and phosphatidylserine/phosphatidylcholine can be solubilized in isooctane. The photolability of the aqueous protein when subjected to irradiation at 280 nm is suppressed in the isooctane-soluble complex. 5. Phosphatidylserine brings about a rapid (t 1/2 is about 150 ms at a lipid concentration of 0.75 mM) dissociation of the linear aggregates formed between the enzyme oligomers. 6. A model of the enzyme-lipid-membrane complex, consistent with these results, is proposed. It is suggested that the enzyme is an allotopic protein and that the dissociation of the enzyme in vitro may involve binding sites on the protein which are designed for interaction with the cardiolipin of the inner mitochondrial membrane, when the enzyme is in the mitochondrial matrix.

Ammonium Chloride↗

A method for 13C enrichment of phospholipid acyl chains using Tetrahymena.

A method has been devised for obtaining highly 13C enriched (20-25%) phospholipids and membranes from the ciliate Tetrahymena, the enrichment occurring in the acyl chains. This method provides both phosphatidylcholine and phosphatidylethanolamine with enriched chains. The central feature of the method is the monoaxenic growth of Tetrahymena on an E. coli mutant which has a high incorporation of exogenous acetate into fatty acid chains. The 13C NMR spectra of the phospholipids are sufficiently enriched to permit NMR relaxation studies.

Acetates↗