Biomedical subjects

S M Humphrey

Publications and source records attributed to S M Humphrey.

At least 19 recordsLinked to original sources

PubMed2000

The NLM Indexing Initiative.

The objective of NLM's Indexing Initiative (IND) is to investigate methods whereby automated indexing methods partially or completely substitute for current indexing practices. The project will be considered a success if methods can be designed and implemented that result in retrieval performance that is equal to or better than the retrieval performance of systems based principally on humanly assigned index terms. We describe the current state of the project and discuss our plans for the future.

Abstracting and Indexing↗

PubMed1995

Metastatic adenocarcinoma mimicking unilateral sacroiliitis.

Back pain is a common clinical syndrome that may be the expression of an uncommon pathological process. We describe an unusual case of adenocarcinoma mimicking unilateral sacroiliitis. When progressive symptoms are unresponsive to conventional therapy, diagnosis should always be reconsidered, with appropriate imaging studies. We discuss mechanisms of joint space involvement and review the literature.

Adenocarcinoma↗

PubMed1991

Influence of storage volume on functional recovery and metabolism of explanted hearts following cold cardioplegia: studies in the rat.

STUDY OBJECTIVE: The aim was to characterise the metabolic and functional recovery after extended periods of hypothermic storage of hearts in varying volume of oxygenated cardioplegic solution. DESIGN: Explanted rat hearts were arrested with and stored in 5, 10, or 100 ml of oxygenated (95% O2: 5% CO2) St Thomas's Hospital cardioplegic solution No 2 (STH) at 4 degrees C for 5 or 10 h. The isolated working heart model was used to determine the cardiac functions and the degree of functional recovery was expressed as a percentage of the prearrest value. Groups of hearts (n = 6) were rapidly freeze-clamped immediately after arrest, at end of storage, or after 30 min reperfusion for quantitation of the high energy phosphate content. SUBJECTS: 84 Male albino Wistar rats weighing 280 to 320 g (heart weight = 1.25 g) were used. MEASUREMENTS AND MAIN RESULTS: All hearts in the three different volumes of STH recovered 80% or more [mean 90 (SEM 3)%] of their prearrest aortic output after 5 h storage but after 10 h, recovery was significantly reduced [23(7)%] with no significant difference among groups. During 5 h storage the phosphocreatine content of the hearts rapidly declined from 33.2(3.1) to 5.0(0.2) mumol.g-1 dry wt in the 5 ml group but only to 16.7(1.2) mumol.g-1 dry wt in the 100 ml group. Similarly ATP preservation was improved in the latter group (81% v 63%, p less than 0.02). Extending the storage time to 10 h resulted in a further decline in high energy phosphates (ATP + phosphocreatine) to 30% of normal values in the 100 ml group and to 9% in the 5 ml group (p less than 0.01). While the total nucleotide pool did not decrease the major catabolite was inosine monophosphate (IMP) which comprised 46% of the nucleotide pool in all groups. The extent of cardiac function recovered was correlated inversely with tissue IMP (R = 0.859) and positively with ATP (R = 0.835) but showed no significant correlations with the postischaemic ADP, AMP, or phosphocreatine. CONCLUSIONS: Increased storage volume of oxygenated cardioplegic solution is superior in the preservation of ATP and phosophocreatine content in donor hearts with full recovery of cardiac function after the first 5 h of hypothermic (4 degrees C) storage.

Adenosine Triphosphate↗

PubMed1991

NMR-visible ATP and Pi in normoxic and reperfused rat hearts: a quantitative study.

Nuclear magnetic resonance (NMR) spectroscopy detects only free, unbound metabolites. We have therefore compared the free high-energy phosphate content of isolated perfused rat hearts (determined by 31P-NMR) with the total high-energy phosphates of the same hearts (determined by chemical analysis) to determine the fractions, if any, that are NMR invisible. Aerobic perfusion (40 min at 37 degrees C, Pi-free Krebs buffer) was followed by 10, 14, or 18 min total global ischemia and 30 min reperfusion (n = 6 in each group). Fully relaxed 31P-NMR spectra (40 scans using 90 degrees pulses at 15-s intervals) were collected at various times throughout the protocol, and the signal intensities of the beta-phosphate of ATP, phosphocreatine (PCr), and Pi were quantified using methylenediphosphonate as an external standard. Hearts were freeze clamped either before ischemia or at the end of reperfusion and were chemically assayed for ATP, PCr, and Pi. After 40 min of normoxia, the ATP and PCr contents determined by NMR were almost identical to the values determined by chemical analysis. However, only 39 +/- 8% of the total Pi was NMR visible. After reperfusion, after 14 or 18 min of ischemia, the proportion of NMR-visible ATP had decreased to 64 +/- 9% (P less than 0.005). After reperfusion after 18 min ischemia, the proportion of NMR-visible Pi had increased to 76 +/- 10% (P less than 0.05). In conclusion, whereas the total cellular content of PCr is always NMR visible, ischemia-reperfusion can alter the fraction of NMR-visible ATP and Pi.

Adenosine Triphosphate↗

PubMed1990

Subcellular distribution of energy metabolites in the pre-ischaemic and post-ischaemic perfused working rat heart.

Isolated working rat hearts were subjected to 20 min of global ischaemia and either 5 min or 15 min of reperfusion. The subcellular distribution of ATP, ADP, AMP, phosphocreatine and Pi were determined before and after ischaemia by the method of non-aqueous tissue fractionation. Ventricular function and the cytosolic, mitochondrial and ATPase-associated compartmentation of metabolites were measured. After 5 min of reperfusion, only 13 +/- 9% of the pre-ischaemic contractile function was restored compared to 67 +/- 8% after 15 min reperfusion. ATP was reduced in all cellular compartments after 5 min of reperfusion but was only decreased from pre-ischaemic values in the cytosolic compartment after 15 min of reperfusion (17.1 +/- 3.9 nmol/mg vs. 4.3 +/- 1.5 nmol/mg total protein; P less than 0.05). The mitochondrial [ATP]/[ADP] was reduced from a normal value of 4.36 to 1.79 after 5 min but recovered to 4.62 after 15 min of reperfusion. Most of the Pi was located in the mitochondria or with the ATPase fraction of the cell, with only 16% of the total Pi free in the cytosol. This study indicates that the capacity of the heart to recover function may be compromised during early reperfusion by a 59% increase in mitochondrial phosphate content and during late reperfusion by a reduced cytosolic/mitochondrial concentration ratio of both ATP (from 0.85 to 0.19) and phosphocreatine (from 3.9 to 1.24).

Adenosine Diphosphate↗

PubMed1990

The anti-adrenergic effect of adenosine and its blockade by pertussis toxin: a comparative study in myocytes isolated from guinea-pig, rat and failing human hearts.

1. In intact ventricular preparation, adenosine has been shown to reduce the beta-adrenoceptor-induced increase in contraction (the anti-adrenergic effect). In the present study we have investigated this effect of adenosine on isolated ventricular myocytes from failing human heart and normal guinea-pig and rat heart. 2. Adenosine in the absence of beta-adrenoceptor-mediated stimulation had no effect on contraction in human and guinea-pig myocytes but produced a variable effect in rat myocytes. 3. 8-Cyclopentyl 1,3-dipropylxanthine (CPX), a selective A1-receptor antagonist, antagonised the anti-adrenergic effect of adenosine in guinea-pig myocytes. 4. The anti-adrenergic effect of adenosine was greater in guinea-pig than rat myocytes and even more pronounced in cells isolated from failing human heart. 5. Pertussis toxin-pretreatment at 35 degrees C of guinea-pig and human myocytes abolished the anti-adrenergic effect of adenosine. Longer exposure to higher concentrations of pertussis toxin was required for complete abolition in human compared to guinea-pig cells. 6. These results support the suggestion that the adenosine receptors mediating the anti-adrenergic effect of adenosine are of the A1 subtype and are coupled to the inhibitory guanine nucleotide binding protein, Gi/Go. 7. Pertussis toxin pretreatment increased the sensitivity of guinea-pig myocytes to isoprenaline in the absence of adenosine; the EC50 value was decreased by a factor of 10. This suggests that Gi may exert a tonic inhibitory effect on the beta-adrenoceptor/adenylate cyclase interaction in normal myocardium.

Adenosine↗

PubMed1988

Functional and metabolic responses of the isolated rat heart to changes in circulating inorganic phosphate concentration.

Normoxic isolated rat hearts were perfused for 30 or 60 min with Krebs-Henseleit bicarbonate buffer (KHB) (in which the Pi concentration was adjusted to 0, 1.2, 2.4, or 10 mM) in both the presence and the absence of glucose as exogenous substrate. Functional performance and coronary flow were monitored throughout the perfusion period, and at its conclusion tissue high-energy phosphates (HEP), glycogen, Pi, and calcium were determined. In the presence of glucose, both developed pressure and coronary flow were significantly (P less than 0.05) reduced by perfusion with 10 mM Pi, while heart rate and energy status were unchanged. Tissue Pi levels were directly related to perfusate concentrations, with an apparent loss of 34% from hearts perfused with 0 mM Pi and a gain of 27% in hearts perfused with 10 mM Pi (which also caused a highly significant [P less than 0.01] uptake of calcium). HEP (ATP and creatine phosphate [CP]) were decreased after 60 min of perfusion with 0 mM Pi. In the absence of glucose, coronary flow was again significantly reduced by perfusion with 10 mM Pi. HEP were significantly (P less than 0.05) conserved and uptake of Pi and calcium was greater than in the presence of glucose. Equivalent free-Ca2+/normal Pi controls for the 10 mM Pi showed that the observed functional effects were not due to a lowering of perfusate free-Ca2+ by the raised Pi level. The effect on coronary flow appears to involve, primarily, a vasomotor mechanism.

Animals↗

PubMed1988

Transmural differences in the postischemic recovery of cardiac energy metabolism.

After 25 minutes of ischemia, in the isolated rat preparation, hearts fail to reestablish adequate contractile function. To determine whether this failure was associated with a transmural variation in the metabolic response of myocardial cells to reperfusion, the authors subjected hearts to 25 minutes of global ischemia with and without 5 or 20 minutes of reperfusion. After freeze-drying the left ventricular myocardium was divided into subepicardial (EPI) and subendocardial (ENDO) regions before estimating the lactate, total adenine pool metabolites, and creatine phosphate (CP) and phosphate concentrations in each region. Other groups of hearts were perfusion-fixed with glutaraldehyde then injected with nuclear track emulsion to demonstrate that a high proportion of capillaries in both the subendocardial (89%) and subepicardial (95%) myocardium transmitted perfusate after 5 minutes of reperfusion. Reperfusion removed lactate equally from each region. Thus the differences in the capacity of reperfusion of these regions to recover CP (ENDO, 100%; EPI, 168% of preischemic values), to elevate adenosine triphosphate (ATP) (ENDO, 32%; EPI, 63%), or to retain adenosine monophosphate (AMP) (ENDO, 625%; EPI, 277%) were unlikely to be due to regional differences in microvascular function. Despite the better preservation of both structure and metabolism in the subepicardium, there was, during reperfusion, a progressive loss of purine precursors from cells in both regions of the myocardium. These results suggest that the loss of ability of the myocardium to recover significant function after relatively short periods of ischemia is due to their inability, on reperfusion, to synthesise sufficient ATP from the available precursors. This capacity for resynthesis of ATP is lost more rapidly in the subendocardial than in the subepicardial myocardium.

Adenine Nucleotides↗

PubMed1987

Knowledge-based indexing of the medical literature: the Indexing Aid Project.

This article describes the Indexing Aid Project for conducting research in the areas of knowledge representation and indexing for information retrieval in order to develop interactive knowledge-based systems for computer-assisted indexing of the periodical medical literature. The system uses an experimental frame-based knowledge representation language, FrameKit, implemented in Franz Lisp. The initial prototype is designed to interact with trained MEDLINE indexers who will be prompted to enter subject terms as slot values in filling in document-specific frame data structures that are derived from the knowledge-base frames. In addition, the automatic application of rules associated with the knowledge-base frames produces a set of Medical Subject Heading (MeSH) keyword indices to the document. Important features of the system are representation of explicit relationships through slots which express the relations; slot values, restrictions, and rules made available by inheritance through "is-a" hierarchies; slot values denoted by functions that retrieve values from other slots; and restrictions on slot values displayable during data entry.

Abstracting and Indexing↗

PubMed1987

Influence of inhibitors of ATP catabolism on myocardial recovery after ischemia.

The loss of the catabolic products of adenosine triphosphate in the form of purine nucleosides and oxypurines during ischemia and subsequent reperfusion may limit adenine nucleotide regeneration. This study compared the effects of infusion of inhibitors of the major reactions involved in the degradation of adenosine triphosphate to inosine on the postischemic recovery of high energy phosphate and myocardial function. Isolated rat hearts were made totally ischemic after a 5-min infusion of p1,p5-diadenosine pentaphosphate, alpha, beta-methylene adenosine diphosphate, nitrobenzyl-6-thioinosine, or erythro-9-(2-hydroxy-3-nonyl) adenine, which are inhibitors of adenylate kinase, 5'-nucleotidase, adenosine translocase, and adenosine deaminase, respectively. Following 30 min of ischemia, only hearts infused with alpha, beta-methylene adenosine diphosphate recovered significantly better ventricular function than did the control (P less than 0.05), but all hearts had increased adenosine triphosphate and creatine phosphate regeneration (P less than 0.05). The formation and washout of greater than 30% of the total adenine pool metabolites were not prevented by any drug. Nevertheless all manipulations of adenine metabolism resulted in recruitment of high energy phosphate during preischemic infusion which may have potential benefits in elective ischemic arrest.

5'-Nucleotidase↗

PubMed1986

The effects of raised phosphate level on the energy metabolism, contractile function, and fine structure of oxygenated and oxygen-deficient myocardium.

The possible role of inorganic phosphate (Pi) in depressing the contractility of oxygen-deficient myocardium was investigated by examining the effects of 30 mM Pi on the cardiac function and myocardial biochemistry and fine structure in normoxic and anoxic Langendorff-perfused isolated rat hearts. In normoxia, the intracellular Pi level increased three-fold, the ATP content remained normal, and there was moderate loss of glycogen only. Contractile performance (as assessed from systolic pressure recordings) was significantly depressed, as was the heart rate for the first 10 min. The myocardial fine structure showed persistent glycogen, marked relaxation of myofibrils, and a higher incidence of vacuolation than in hearts with normal Pi. In anoxia, the intracellular Pi level was comparable with that of the perfusate and both ATP and glycogen were severely depleted. Contractile performance and heart beat ceased completely at 15 min, although in anoxic controls both persisted at low levels for at least 25 min. In anoxia, Pi also depressed coronary flow rate. In the inner half of the ventricular wall of oxygen-depleted hearts, where flow became reduced after 15 or more min, Pi markedly reduced the formation of intramitochondrial densities and augmented mitochondrial swelling and ischaemic contracture, which extended out through the mid-myocardium. In the outer half of the wall, where flow remained high, it promoted severe dilatation of the sarcoplasmic reticulum vesicles and undifferentiated regions of the intercalated discs. The observed effects in normoxia are probably attributable at least in part to the lowering of the free Ca2+ concentration of the perfusate by the increased Pi level.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

The influence of inhibitors of the ATP degradative pathway on recovery of function and high energy phosphate after transient ischemia in the rat heart.

The loss of the catabolic products of adenosine triphosphate in the form of purine nucleosides and oxypurines during ischemia and subsequent reperfusion may limit adenine nucleotide regeneration. This study compared the effects of infusion of inhibitors of the major reactions involved in the degradation of adenosine triphosphate to inosine on the postischemic recovery of high energy phosphate and myocardial function. Inhibitors of adenylate kinase, 5'nucleotidase, adenosine translocase and adenosine deaminase were studied. Following 30 minutes of ischemia, only hearts infused with alpha, beta, methylene adenosine diphosphate (5' nucleotidase inhibitor) recovered significantly better ventricular function than control (p less than 0.05), but all hearts had increased adenosine triphosphate regeneration (p less than 0.05). The formation and washout of greater than 30% of the total adenine pool metabolites was not prevented by any drug. Nevertheless all manipulations of adenine metabolism resulted in recruitment of high energy phosphate during preischemic infusion.

5'-Nucleotidase↗

PubMed1986

Factors affecting the development of contraction band necrosis during reperfusion of the isolated isovolumic rat heart.

The effects of time, oxygen availability and transmural fibre location on the post-ischaemic development of contraction-band necrosis was investigated in isolated isovolumic rat hearts. Anoxic reperfusion after 60 min of total ischaemia was associated with the slow development of contraction bands (8% of myocytes affected after 20 min), particularly in the circumferentially oriented mid-myocardial muscle fibres. This could be completely prevented by the presence of 3 mM amytal. Oxygenated reperfusion caused a rapid development of contraction bands (6% of myocytes affected after 5 mins) which was significantly (P less than 0.05) increased to 18% of cells affected by 20 mins reoxygenation. The mid-myocardium always contained the greatest number of contraction bands with up to 46% of cells involved after 20 mins of oxygenated reperfusion. In all groups many cells were observed to have disrupted sarcolemmae irrespective of the presence or absence of contraction bands. The predominance of contraction bands in the constrictor muscles encircling the heart suggests that their formation may be influenced by the tension or strain imposed upon myocardial fibres during the ischaemic episodes.

Amobarbital↗

PubMed1985

Myocardial adenine pool depletion and recovery of mechanical function following ischemia.

The loss of nucleotide pool precursors from the heart during ischemia and reperfusion may affect resynthesis of ATP and consequently mechanical recovery. Isolated working rat hearts were made globally ischemic for from 15 to 25 min, and the tissue content of adenine pool metabolites, creatine, creatine phosphate (CP), and inorganic phosphate (Pi), were measured after 20 min of reperfusion. In addition, the coronary effluent was assayed for nucleotides, nucleosides, and oxypurines. Hearts that recovered 75% or more of their preischemic hemodynamic function had significantly lower ATP and NAD but greater CP and Pi than controls. Complete failure of hearts was associated with severely depleted ATP but not CP. All hearts released 25% or more of their preischemic adenine pool during the 20-min reperfusion. This loss correlated more closely with a reduction in recovery from 100 to 75% than with complete failure. Thus extensive loss of adenine pool precursors is not critically related to the failure of heart muscle to recover function but may be an important limiting factor in determining the extent and time course of mechanical recovery.

Adenine↗

PubMed1985

Reversal of the no reflow phenomenon in globally ischemic rat hearts by ventricular dilation.

Changes in the contracture and stiffness of ventricular walls during ischemia and their effect on vascular reperfusion were studied in isolated rat hearts. Global ischemia was induced by stopping the flow of oxygenated perfusate for 60 min. Contracture pressures generated against water-filled left ventricular balloons maintained at diastolic volume increased between 8 and 25 min of ischemia and declined thereafter. On the other hand, left ventricular wall stiffness, estimated from the pressure required to periodically inflate otherwise uninflated balloons to diastolic volume, increased rapidly between 20 and 30 min of ischemia, and more slowly thereafter. Inflation of balloons following 30 or more min of ischemia caused significant reductions in left ventricular wall stiffness. Similar brief inflation after 60 min of ischemia allowed aqueous sodium fluorescein to perfuse the subendocardial half of the left ventricular wall which was otherwise not accessible to reperfusion. This reversal of the no reflow phenomenon was accompanied by a reduction in myocardial wall stiffness, stretching of myocytes and increased patency of myocardial capillaries.

Animals↗

PubMed1985

Effects of anoxic or oxygenated reperfusion in globally ischemic, isovolumic, perfused rat hearts.

It has not previously been possible to study the in vitro effects of reperfusion on severely injured isolated perfused hearts because of the development of the no-reflow phenomenon, concomitant with the onset of irreversible myocardial cell injury. A new model of ischemic injury which utilizes an intraventricular balloon to allow uniform reperfusion of irreversibly damaged hearts is described. The effects of reperfusion were studied in Langendorff perfused rat hearts after no-flow ischemia for 60 and 150 minutes at 37 C. Uniform reflow was facilitated by maintaining the left ventricle at an isovolumic diastolic volume with a balloon during ischemia and removal of the balloon prior to reflow. Reperfusion was with 1) anoxic media, 2) oxygenated media, 3) oxygenated media in the presence of the mitochondrial inhibitor Amytal, or 4) an initial anoxic reperfusion followed by oxygenated media. Injury was monitored by the assay of released creatine kinase (CK) and myoglobin (Myo), by light-microscopic estimates of the percent of cells containing contraction bands, and by ultrastructural changes. CK and Myo were released with anoxic reperfusion, but larger releases occurred with oxygenated reperfusion. Amytal inhibited the oxygen but not the nitrogen component of release. Contraction bands occurred following oxygenated, but not anoxic, reperfusions and were inhibited by Amytal. Following an initial anoxic reperfusion, oxygen caused additional CK and Myo release and produced an increase in the percent of cells with contraction bands, compared with that with oxygen alone. The response of cells to injury was heterogeneous, and the hearts contained cells with a spectrum of ultrastructural changes. Anoxic reperfusion was associated with cellular swelling and oxygenated reperfusion with contraction band necrosis.

Amobarbital↗

PubMed1984

File maintenance of MeSH headings in MEDLINE.

This article addresses file maintenance of subject headings in the National Library of Medicine's MEDLINE, a bibliographic retrieval file which is indexed using Medical Subject Headings (MeSH), NLM's subject authority. The emphasis is class maintenance in which sets of records in MEDLINE are changed by maintenance actions which reflect yearly changes in MeSH. Specific types of maintenance action are described with examples to highlight problem areas. Class maintenance failures, checking class maintenance, and informing end-users of MeSH changes resulting in class maintenance are discussed. Technical constraints and feasibility are not analyzed in detail; rather, the approach is geared toward requirements and impact of maintenance from the standpoint of vocabulary specialists and end-users. The article concludes with a brief statement on defining file maintenance policy.

MEDLARS↗

PubMed1984

The influence of the no-reflow phenomenon on reperfusion and reoxygenation damage and enzyme release from anoxic and ischaemic isolated rat hearts.

Eighty isolated rat heart preparations were used to study relationships among creatine kinase (CK) release, the loss of vascular competence (no-reflow), and the distribution of morphological changes across the left ventricular wall which occur during 60 min global ischaemia or anoxia and following subsequent oxygenated reperfusion. Hearts were either fixed with glutaraldehyde for light and electron microscopy or were injected with 1% fluorescein to define the distribution of perfusable vessels. The extent of no-reflow in half of the hearts was reduced experimentally by maintaining the diastolic volume of the left ventricular lumen during ischaemia and anoxia with a water-filled balloon. The amount of CK released during 20 min of reoxygenation or reperfusion was inversely proportional to the extent of the no-reflow area observed just prior to reoxygeneration, and also reflected the transmural extent and the severity of myocardial cell damage. Extensive contraction band necrosis was only observed in reperfused regions of anoxic hearts. In isovolumic hearts reoxygenation caused no-reflow to develop in the ventricular myocardium, and this appeared to be associated with hypercontraction. Thus the no-reflow phenomenon has a profound effect on the transmural distribution of myocardial cell damage and enzyme release which follows post ischaemic reperfusion and post anoxic reoxygenation.

Animals↗