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Biomedical subjects

A J Anderson

Publications and source records attributed to A J Anderson.

At least 91 records · Page 5Linked to original sources
PubMed1991

Continuous intravenous infusion of morphine for severe dyspnea.

We describe eight patients who had terminal lung cancer causing severe dyspnea unrelieved by oxygen, nonnarcotic drugs, or intermittent bolus narcotics. We treated these patients with continuous intravenous infusion of morphine, beginning with bolus IV injections of 1 or 2 mg of morphine every 5 to 10 minutes until the patient reported relief. A continuous morphine infusion was then started, with the hourly dose equal to 50% of the cumulative bolus dose. Vital signs, degree of sedation, and blood gases were serially followed. Six patients achieved good dyspnea relief, one had moderate relief, and one had a poor response. Variable changes were noted in the PaO2, whereas PaCO2 steadily increased in five of seven patients, and pH decreased in six. There was little change in systolic blood pressure or pulse, and only one individual had less than 10 respirations per minute. The major side effect of treatment was sedation, treated by temporarily discontinuing morphine until the patients' mental status improved and then restarting the infusion at a 50% lower hourly morphine dose. Mean time of study was 30 hours (range 16 to 87 hours). Seven of the eight study patients died during treatment. Whether morphine therapy shortened survival is uncertain. We conclude that continuous morphine infusion is effective therapy for severe dyspnea. The treatment is ethically justified. Relief of suffering is the primary goal of therapy, and less risky treatments are unavailable.

Aged↗
PubMed1991

When is it safe not to replace an implantable cardioverter defibrillator generator?

In most reports on patients receiving implantable cardioverter defibrillators, shocks were received mainly during the first 2 to 3 years. Thus, the question had been raised as to the need for device replacement after 3 or 4 years if no shocks had been received. In order to answer this question, shock experience in 184 patients receiving the implantable cardioverter defibrillator was analyzed. Patients were followed for a mean of 24 +/- 18.7 months. A patient's shock was judged to be appropriate if there was electrocardiographic documentation of sustained ventricular tachyarrhythmia at the time of shock or if it was preceded by sudden onset of presyncopal or syncopal symptoms. The majority of patients had coronary artery disease. In approximately two-thirds of patients, left ventricular ejection fraction was below 40%. One hundred fourteen patients had inducible sustained monomorphic ventricular tachycardia. On follow-up, there were 29 deaths, five of which were sudden. Sixty-eight patients received an appropriate shock during follow-up (37%). Over 90% of these 68 received their first shock within the 2 years after implant. The actuarial risk of receiving an appropriate shock by the fifth year after implant was 69%. Conversely, 31% of patients who survived 5 years had not received an appropriate shock. Hazard analysis indicates that there is a high incidence of first appropriate shock during the year following implant. Subsequently, the incidence dropped to a relatively steady rate with a rise in this rate during the fifth year. This analysis suggested a bimodal distribution of appropriate shocks.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1991

Does reception of appropriate shocks from the implantable cardioverter defibrillator affect survival?

The implantable cardioverter defibrillator has become an important therapeutic modality for treatment of life-threatening ventricular tachyarrhythmias. Recent reports have suggested that patients who receive appropriate shocks from this device have an inordinately high overall mortality, and questioned the extent of benefit these patients derive from the implant. This report analyzed the survival among 184 patients who received the implantable cardioverter defibrillator to assess survival differences between patients who received appropriate shocks versus those who did not. At a mean follow-up of 24 +/- 18.7 months, 68 patients received an appropriate shock from their device while 116 did not receive an appropriate shock. Overall survival of the entire population was quite similar to those published by others. There was no significant difference between overall survival of patients who received an appropriate shock versus those who did not. However, there was a statistically significant difference in sudden death mortality. The group of patients that received appropriate shocks included all five sudden deaths. This observation suggested that sudden death in this population was likely due to ventricular tachyarrhythmias rather than strictly bradycardia or asystole. The "benefit" of the device to the entire population was also assessed by estimating survival after receipt of the first appropriate shock. Using this approach, an estimated 10% of patients died without receiving an appropriate shock. In other words, ultimately, 90% of patients were expected to benefit from the device. This survival curve, which initiated only after receipt of the first appropriate shock was fairly similar to those estimated from conventional methods. Therefore, survival after receipt of an appropriate shock was comparable to overall survival and there was no significant difference between survival of patients who received appropriate shocks and those who did not.

Death, Sudden, Cardiac↗
PubMed1990

Biosynthesis and composition of bacterial poly(hydroxyalkanoates).

It is well established that Alcaligenes eutrophus can accumulate a copolymer containing 3-hydroxybutyrate and 3-hydroxyvalerate, but longer 3-hydroxyacid monomers have not been reported to occur in this organism. The properties of the enzymes of poly(hydroxyalkanoate) (PHA) biosynthesis are discussed and it is proposed that the substrate specificity of the polymerizing enzyme restricts the range of monomer units incorporated into PHA. Various other bacteria produce similar copolymers from propionic acid and/or valeric acid. A number of Pseudomonas species accumulate PHAs containing longer-chain monomer units from linear alkanoic acids, alkanes and alcohols.

Alcaligenes↗
PubMed1990

Pertussis toxin-sensitive G-protein activation does not influence the response to Bay K 8644 in embryonic chick myocytes.

Pretreatment of embryonic chick cardiac myocytes with pertussis toxin (1-2.5 micrograms ml-1 for 22 h) abolished the negative chronotropic effects of carbachol but not the positive inotropic effects of Bay K 8644. Neither guanosine 5'-O-3-thiotriphosphate (GTP gamma S 500 microM intracellularly), nor pertussis toxin (0.5-1 microgram ml-1 for 22 h) modified the agonist effects of Bay K 8644 on calcium channel currents recorded under whole-cell voltage clamp. These findings indicate that pertussis-sensitive guanine nucleotide binding (G)-proteins does not modulate the effects of calcium channel activators in embryonic chick cardiac myocytes.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

RS 30026: a potent and effective calcium channel agonist.

1. A series of dihydropyridine derivatives has been evaluated for calcium channel agonist activity using reversal of nisoldipine-induced inhibition of beating of aggregates of embryonic chick myocytes. This test appears to be specific for calcium channel agonists since isoprenaline and cardiac glycosides are inactive. 2. RS 30026 was the most potent of the series, was significantly more potent than CGP 28392 and of similar potency to Bay K 8644 (pEC50 = 7.45, 6.16 and 7.20, respectively). RS 30026 increased edge movement of individual aggregates, in the absence of nisoldipine, by 50% at 2 nM. 3. Compounds were also evaluated for their effects on guinea-pig papillary muscle and porcine coronary artery rings. RS 30026 displayed positive inotropism at concentrations between 10(-9) and 10(-6) M (pEC200 = 8.21), but was a much more powerful inotrope than Bay K 8644, increasing contractility to 1300% of control at 10(-6) M (compared to 350% of control for Bay K 8644). RS 30026 caused vasoconstriction at concentrations between 10(-10) and 10(-7) M. 4. Calcium channel currents in single embryonic chick myocytes were recorded by whole-cell voltage clamp techniques. RS 30026 (100 nM-500 nM) produced large increases in peak current amplitude and shifted the voltage for threshold and maximal currents to more negative values. RS 30026 (500 nM) also produced large increases in the inward tail currents evoked upon repolarization. The effects of Bay K 8644 (50 and 500 nM) were much less marked. 5. Analysis of the activation characteristics of currents showed parallel shifts in the activation curve to more negative potentials in the presence of 50 nm Bay K 8644, with a much smaller shift in the presence of 500nm Bay K 8644. RS 30026 (100 and 500nM) caused concentration-dependent shifts in the activation of the calcium channel currents with an increase of the slope of the curve. 6. RS 30026 appears to be the most potent and effective calcium channel agonist described to date.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Accumulation of a Polyhydroxyalkanoate Containing Primarily 3-Hydroxydecanoate from Simple Carbohydrate Substrates by Pseudomonas sp. Strain NCIMB 40135.

A number of Pseudomonas species have been identified which accumulate a polyhydroxyalkanoate containing mainly 3-hydroxydecanoate monomers from sodium gluconate as the sole carbon source. One of these, Pseudomonas sp. strain NCIMB 40135, was further investigated and shown to accumulate such a polyhydroxyalkanoate from a wide range of carbon sources (C(2) to C(6)); however, when supplied with octanoic acid it produced a polyhydroxyalkanoate containing mainly 3-hydroxyoctanoate monomers. Polymer synthesis occurred in batch culture after cessation of growth due to exhaustion of nitrogen. In continuous culture under nitrogen limitation up to 16.9% (wt/wt) polyhydroxyalkanoate was synthesized from glucose as the carbon source. The monomer units are mainly of the R-(-) configuration. Nuclear magnetic resonance studies confirmed the composition of the polymer. Differential scanning calorimetry suggested that the solvent-extracted polymer contained a significant proportion of crystalline material. The weight-average molecular weight of the polymer from glucose-grown cells was 143,000.

Journal Article↗
PubMed1990

Catalase and superoxide dismutase of root-colonizing saprophytic fluorescent pseudomonads.

Root-colonizing, saprophytic fluorescent pseudomonads of the Pseudomonas putida-P. fluorescens group express similar levels of catalase and superoxide dismutase activities during growth on a sucrose- and amino acid-rich medium. Increased specific activities of catalase but not superoxide dismutase were observed during growth of these bacteria on components washed from root surfaces. The specific activities of both enzymes were also regulated during contact of these bacteria with intact bean roots. Increased superoxide dismutase and decreased catalase activities were observed rapidly, by 10 min upon inoculation of cells onto intact bean roots. Catalase specific activity increased with time to peak at 12 h before declining. By 48 h, the cells displayed this low catalase but maintained high superoxide dismutase specific activities. Catalase with a low specific activity and a high superoxide dismutase activity also were present in extracts of cells obtained from 7-day-old roots colonized from inoculum applied to seed. This specific activity of superoxide dismutase of root-contacted cells was about fourfold-higher in comparison to cells grown on rich medium, whereas the specific activity for catalase was reduced about fivefold. A single catalase isozyme, isozyme A, and one isozyme of superoxide dismutase, isozyme 1, were detected during growth of the bacteria on root surface components and during exposure of cells to intact bean roots for 1 h. An additional catalase, isozyme B, was detected from bacteria after exposure to the intact bean roots for 12 h. Catalase isozyme A and superoxide dismutase isozyme 1 were located in the cytoplasm and catalase band B was located in the membrane of P. putida.

Journal Article↗
PubMed1990

Occurrence, metabolism, metabolic role, and industrial uses of bacterial polyhydroxyalkanoates.

Polyhydroxyalkanoates (PHAs), of which polyhydroxybutyrate (PHB) is the most abundant, are bacterial carbon and energy reserve materials of widespread occurrence. They are composed of 3-hydroxyacid monomer units and exist as a small number of cytoplasmic granules per cell. The properties of the C4 homopolymer PHB as a biodegradable thermoplastic first attracted industrial attention more than 20 years ago. Copolymers of C4 (3-hydroxybutyrate [3HB]) and C5 (3-hydroxyvalerate [3HV]) monomer units have modified physical properties; e.g., the plastic is less brittle than PHB, whereas PHAs containing C8 to C12 monomers behave as elastomers. This family of materials is the centre of considerable commercial interest, and 3HB-co-3HV copolymers have been marketed by ICI plc as Biopol. The known polymers exist as 2(1) helices with the fiber repeat decreasing from 0.596 nm for PHB to about 0.45 nm for C8 to C10 polymers. Novel copolymers with a backbone of 3HB and 4HB have been obtained. The native granules contain noncrystalline polymer, and water may possibly act as a plasticizer. Although the biosynthesis and regulation of PHB are generally well understood, the corresponding information for the synthesis of long-side-chain PHAs from alkanes, alcohols, and organic acids is still incomplete. The precise mechanisms of action of the polymerizing and depolymerizing enzymes also remain to be established. The structural genes for the three key enzymes of PHB synthesis from acetyl coenzyme A in Alcaligenes eutrophus have been cloned, sequenced, and expressed in Escherichia coli. Polymer molecular weights appear to be species specific. The factors influencing the commercial choice of organism, substrate, and isolation process are discussed. The physiological functions of PHB as a reserve material and in symbiotic nitrogen fixation and its presence in bacterial plasma membranes and putative role in transformability and calcium signaling are also considered.

Bacteria↗
PubMed1990

Body fat distribution and male/female differences in lipids and lipoproteins.

The role of body fat distribution, as assessed by the ratio of waist-to-hip circumferences (WHR), in statistically explaining differences in levels of lipoproteins between men and women was studied using data collected in 1985-1986 from employed adults (mean age, 40 years). As compared with the 415 women, the 709 men had higher mean levels of triglycerides (+38 mg/dl) and apolipoprotein B (+11 mg/dl) as well as lower mean levels of high density lipoprotein (HDL) cholesterol (-15 mg/dl) and apolipoprotein A-I (-19 mg/dl). Additionally, men were more overweight, consumed more alcohol, and exercised more frequently than women but were less likely to smoke cigarettes. Controlling for these characteristics, however, did not alter the differences in lipoprotein levels between men and women. In contrast, adjustment for WHR (which was greater among men) reduced the sex differences in levels of apolipoprotein B (by 98%), triglycerides (by 94%), HDL cholesterol (by 33%), and apolipoprotein A-I (by 21%). Similar results were obtained using analysis of covariance, stratification, or matching; at comparable levels of WHR, differences in lipid and lipoprotein levels between men and women were greatly reduced. Although these results are based on cross-sectional analyses of employed adults and need to be replicated in other populations, the findings emphasize the relative importance of body fat distribution. Whereas generalized obesity and body fat distribution are associated with lipid levels, fat distribution (or a characteristic influencing fat patterning) can be an important determinant of sex differences in levels of triglycerides, HDL cholesterol, and apolipoproteins B and A-I.

Adipose Tissue↗
PubMed1989

Improved early results after aortic valve replacement: analysis by surgical time frame.

Primary aortic valve replacement was performed in 430 patients. It was an isolated procedure in 339 and was combined with coronary artery bypass grafting in 91. Of these patients, 282 underwent operation from 1970 through 1976 (time frame 1) and 148 from 1980 through 1985 (time frame 2). They were divided into subgroups by age, New York Heart Association functional class, combined coronary artery bypass graft, and valvular lesion. Overall hospital mortality was 7.7% (time frame 1 = 10.6% versus time frame 2 = 2.0%; p less than 0.01). Overall, functional class III or IV was the strongest predictor of hospital mortality (p less than 0.001). Association of coronary artery bypass graft was the next strongest predictor of hospital mortality (p less than 0.01), and it retained its predictive value in time frame 2. Overall, hospital mortality was higher in patients older than 55 years (10.5% versus 3.5%; p less than 0.05). There were no hospital deaths in patients younger than 55 years in time frame 2. Type of valvular lesion was not a predictor of hospital mortality. Hospital mortality in patients receiving cardioplegia was 2%. Cardioplegia use has lessened the effect of age and functional class as predictors of hospital mortality after primary aortic valve replacement. Earlier operation in time frame 2 played a substantial role in the overall improvement of early results.

Adult↗
PubMed1989

Risk factors and the anatomic distribution of coronary artery disease.

Differences in the importance of risk factors according to the anatomic location of coronary artery disease (CAD) were assessed in 4722 men and 1069 women who underwent arteriography. Examined characteristics included total and high-density lipoprotein (HDL)-cholesterol, triglycerides, obesity, smoking, alcohol consumption, diabetes, and hypertension. Of these risk factors, the ratio of total to HDL-cholesterol showed the highest correlation with the overall severity of CAD (r = 0.24, men; r = 0.38, women); in contrast, its relation to left main (LM) disease was much lower (r = 0.10, men; r = 0.08 women) than were correlations with stenotic disease in the left anterior descending, circumflex, and right coronary arteries. Other risk factors also showed weaker associations with LM disease than with stenoses in other vessels, and none was related to increased LM disease after controlling for disease in other vessels. For example, as compared with men who had no significant CAD, those with 1-, 2-, and 3-vessel disease had mean increases in total cholesterol of 12, 18, and 19 mg/dl, respectively. In contrast, after adjusting for disease in other vessels, LM disease (present in 293 men) was associated with only a 4 mg/dl increase in mean cholesterol levels (P = 0.20). These results indicate that the relation of risk factors to CAD differs according to the location of the stenotic disease, and that LM disease is poorly predicted by the standard risk factors.

Adult↗
PubMed1989

Factors influencing the transfusion response to HLA-selected apheresis donor platelets in patients refractory to random platelet concentrates.

Immune and nonimmune causes of platelet refractoriness were evaluated in a group of patients receiving HLA-selected single-donor platelet transfusions. During a 1-year observation period, 1 h and 24 h platelet recoveries wre determined after 522 single-donor platelet transfusions given to 43 patients persistently refractory to pooled random-donor platelet transfusions. 72% of patients tested ultimately developed lymphocytotoxic antibodies suggesting they were alloimmunized. When significant lymphocytotoxic antibodies were demonstrable in these patients, HLA well-matched platelet transfusions consistently produced good transfusion responses. In contrast, patients without lymphocytotoxic antibodies had clinical factors that adversely affected transfusion outcome (P less than 0.0001). Fever and splenomegaly markedly reduced 1 h post-transfusion platelet recoveries, while sepsis compromised the 24 h platelet recovery. Overall, the presence of any clinical factor was most likely to reduce 1 h platelet recovery, while donor-recipient HLA incompatibilities correlated best with poor 24 h post-transfusion platelet recovery. A platelet crossmatch test predicted the transfusion response when non-immune clinical factors were absent.

Antilymphocyte Serum↗
PubMed1989

Response of plant-colonizing pseudomonads to hydrogen peroxide.

Colonization of plant root surfaces by Pseudomonas putida may require mechanisms that protect this bacterium against superoxide anion and hydrogen peroxide produced by the root. Catalase and superoxide dismutase may be important in this bacterial defense system. Stationary-phase cells of P. putida were not killed by hydrogen peroxide (H(2)O(2)) at concentrations up to 10 mM, and extracts from these cells possessed three isozymic bands (A, B, and C) of catalase activity in native polyacrylamide gel electrophoresis. Logarithmic-phase cells exposed directly to hydrogen peroxide concentrations above 1 mM were killed. Extracts of logarithmic-phase cells displayed only band A catalase activity. Protection against 5 mM H(2)O(2) was apparent after previous exposure of the logarithmic-phase cells to nonlethal concentrations (30 to 300 muM) of H(2)O(2). Extracts of these protected cells possessed enhanced catalase activity of band A and small amounts of bands B and C. A single form of superoxide dismutase and isoforms of catalase were apparent in extracts from a foliar intercellular pathogen, Pseudomonas syringae pv. phaseolicola. The mobilities of these P. syringae enzymes were distinct from those of enzymes in P. putida extracts.

Journal Article↗
PubMed1989

Cigarette smoking and non-fatal myocardial infarction in women: is the relation independent of coronary artery disease?

The relation of cigarette smoking to both coronary disease and non-fatal myocardial infarction was examined in a cross sectional study of 1053 women who underwent coronary arteriography. As compared with the 489 women who had never smoked cigarettes, ever-smokers (mean duration of smoking, 25 years) were 1.6 times as likely to have significant stenotic disease and were 1.9 times as likely to have suffered a myocardial infarction. These associations were strongest in women under 50 years of age, with odds ratios of 3.5 for coronary artery disease and 4.5 for myocardial infarction. Although the extent of stenotic disease and prior myocardial infarction were strongly associated, women who smoked cigarettes remained at increased risk of a myocardial infarction even after their increased coronary artery disease had been taken into account. For example, heavy smokers (greater than 30 pack-years) were 2.3 times as likely to have had a myocardial infarction as were non-smokers; controlling for the extent of stenotic disease (in addition to age and other risk factors) reduced the estimated relative risk to only 1.9. Stratified analyses showed that this increased risk for clinical disease among smokers was evident at all levels of occlusion, even among women with minimal stenotic disease. These results, collected at the time of arteriography, suggest that non-atherogenic mechanisms may be important in the aetiology of myocardial infarction among women who smoke cigarettes.

Coronary Artery Disease↗
PubMed1989

Thrombosis: the major Hickman catheter complication in patients with solid tumor.

Major complications of Hickman catheter placement (thrombosis and infection) were determined in 168 patients with solid tumor (lung, 79; head and neck, 56; esophagus, 24; and miscellaneous, 9). Catheter-related thrombosis was clinically detected in 22 individuals and was detected at autopsy in six (total 17 percent). The 17 percent figure underestimates the true incidence of thrombosis since only 25 percent of study patients had autopsies. Patients with adenocarcinoma of the lung constituted a high risk group. Nine of 20 (45 percent) of these patients had thrombosis compared to 25, 9, and 16 percent of patients with squamous cell cancers of lung, head and neck and esophagus, respectively (p less than 0.002). Three patients with thrombosis had pulmonary emboli and two died. Thrombosis occurred despite daily heparin catheter flushing. INfections occurred in 11 patients. One had suspected endocarditis, one had a subcutaneous tunnel infection, and nine had exit site infections. All responded to local or systemic antibiotics. Better methods to prevent thrombosis are needed.

Adenocarcinoma↗