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Leukotriene D4 (2 c 10(-9) mole), injected into the left circumflex coronary artery of anesthetized sheep, produced profound coronary vasoconstriction and impaired regional ventricular wall motion. This cardiac effect was neither inhibited by prior treatment of the sheep with a cyclooxygenase inhibitor nor associated with thromboxane B2 release into the coronary sinus. Intravenous FPL 55712 completely abolished the coronary vasoconstriction of leukotriene D4, but a significant reduction of regional wall shortening persisted.

Arterial blood nitrogen tensions of free-diving Weddell seals (Leptonychotes weddelli) were measured by attaching a microprocessor-controlled blood pump and drawing samples at depth to determine how these marine mammals dive to great depths and ascend rapidly without developing decompression sickness. Forty-seven samples of arterial blood were obtained from four Weddell seals during free dives lasting up to 23 minutes to depths of 230 meters beneath the sea ice of McMurdo Sound, Antarctica. Peak arterial blood nitrogen tensions of between 2000 and 2500 millimeters of mercury were recorded at depths of 40 to 80 meters during descent, indicating that the seal's lung collapses by 25 to 50 meters. Then arterial blood nitrogen tensions slowly decreased to about 1500 millimeters of mercury at the surface. In a single dive, alveolar collapse and redistribution of blood nitrogen allow the seal to avoid nitrogen narcosis and decompression sickness.

A visual-imagery mnemonic was used as a memory training aid for a 66-year-old patient with primary degenerative dementia. Length of retention time was used as the primary outcome measure. The application of the mnemonic procedure extended the length of retention time for name-face recall from baseline. Performance gains were sustained at one month.

A prevalence survey for known diabetes was conducted in a geographically defined population of nearly 40,100 in Oxford in April 1982. The age-adjusted prevalence rate was 10.4/1000 which did not differ significantly from age-adjusted rates of 9.5/1000 in Poole and 10.5/1000 in Southall. The prevalence increased with age and was higher in men than women over the age of 30 years. Our results confirm that there has been a change in the male to female sex ratio and suggest that there are about 500,000 diagnosed diabetics in England and Wales including about 190,000 insulin-treated patients. These findings are consistent with a secular increase in the prevalence of diagnosed diabetes over the last two decades which has important implications for the planning and provision of resources for care.

Complications of MI occur in patients of all ages, but are more common in the elderly. Prevalent are atrial and ventricular dysrhythmias, papillary muscle dysfunction, pericarditis, congestive heart failure, atrioventricular block, cardiogenic shock, and myocardial rupture. Improved surgical techniques and methods of myocardial protection have reduced the perioperative mortality of coronary artery bypass surgery in older persons to an acceptable level.

We evaluated the efficacy of the Stanford Quit Kit, an eight-page self-administered smoking cessation program. Subjects were randomly assigned to receive the Quit Kit (n = 142) or a delayed intervention (n = 65). Confirmed abstinence (p less than .05) and reduced smoking among continuing smokers (p less than .002) were greater in the Quit Kit group than in the control group at the two-month follow-up. At the six-month follow-up 10.6 percent of the Quit Kit subjects were confirmed as abstinent. From these results we conclude that well-designed, self-administered behavior change materials can assist chronic smokers in quitting.

A brief battery of psychometric tests was used to compare 41 individuals with very mild senile dementia of the Alzheimer type (SDAT) with 83 healthy participants and 66 individuals with mild SDAT. Although canonical analysis indicated that the same psychological functions (memory, speeded psychomotor performance, and language) are involved in both very mild and mild SDAT, objective levels of performance by the very mildly affected individuals overlapped extensively with those of both healthy aged and mildly demented individuals. Consideration of premorbid individual differences in psychological functions will probably be required if psychometric test performances are to be effective in detecting SDAT in the very mild stage.

In this report, the authors present the results of 34 estimates of pulmonary capillary pressure (Pcap) in 15 adult patients receiving intensive care for acute respiratory failure (ARF). Within the pulmonary artery pressure profile during transient balloon occlusion, the authors identified two exponential pressure decay components-the slower one representing the discharge of the pulmonary capillary pressure through the pulmonary venous resistance. By extrapolating this exponential to its origin at the moment of pulmonary artery occlusion, a pressure within the pulmonary vascular bed which approximates pulmonary capillary pressure (Pcap) was identified. Pcap, and not the pulmonary artery occlusion pressure (PAOP), is the major driving pressure forcing fluid from the pulmonary microvasculature. The results indicate that a discrete value for pulmonary capillary pressure can be reproducibly measured in paralyzed ventilated patients. The data report that mean pulmonary artery pressure, pulmonary capillary pressure, and total pulmonary vascular resistance (PVR) are increased in acute respiratory failure, but there is considerable variation in the distribution of pulmonary vascular resistance between the arterial and venous beds. The data suggest that there is unequal and variable partitioning of the increased PVR during acute respiratory failure. Bedside pressure profile Pcap measurements will allow optimum reduction of Pcap during ARF by infusing vasoactive agents to modify the distribution of PVR or reducing the PAOP.

The present study examined the residual effects of smoking status on cognitive function in 76 nondemented older adults. Current smokers, ex-smokers, and nonsmokers who were screened for health and intellectual impairments were administered a battery of standardized neuropsychological tests to measure problem solving, psychomotor speed, memory, attention span, perception, and language production. Performance decrements were found for smokers on measures of psychomotor speed. No between-group differences were noted on any of the nonspeeded tests. There were no differences between nonsmokers and ex-smokers on any measures. The results suggest that the residual effects of current cigarette smoking negatively influence speeded cognitive capabilities in older adults.

Fifteen minutes after intravenous Escherichia coli endotoxin (EN) infusion the sheep lung transiently releases into the systemic circulation up to 12 micrograms of thromboxane A2 (TxA2)/min measured by radioimmunoassay as its metabolite thromboxane B2 (TxB2). To determine whether lung thromboxane release alters regional blood flow (RBF) we injected microspheres before and 20, 30, and 100 minutes after EN infusion in 13 awake sheep. In seven untreated control sheep (group 1) pulmonary vascular resistance (PVR) increased threefold at 20 and 30 minutes after EN infusion, coinciding with a large transpulmonary blood concentration gradient of TxB2. There was no measured RBF change to any systemic tissue or organ except the right ventricle at 20 minutes after EN infusion, when blood flow per gram of tissue doubled. In six sheep (group 2) treated with intravenous ibuprofen before EN infusion there was no increase in PVR, plasma TxB2, or blood flow to the right ventricle, and no difference of RBF to any other organ or tissue when compared to group 1. TxA2 is a potent local pulmonary vasoconstrictor but it rapidly hydrolyzes. Its short half-life and the circulatory delay in systemic arterial delivery prevent TxA2 from acting as a circulating vasoconstrictor.

An inhibitor of malted barley (Hordeum vulgare cv Conquest) alpha-amylase II was purified 125-fold from a crude extract of barley kernels by (NH(4))(2)SO(4) fractionation, ion exchange chromatography on DEAE-Sephacel, and gel filtration on Bio-Gel P 60. The inhibitor was a protein with an approximate molecular weight of 20,000 daltons and an isoelectric point of 7.3. The protein was homogeneous, as assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Amino acid analysis indicated the presence of about 9 half-cystine residues per mole. The neutral isoelectric point of the inhibitor suggested that some of the apparently acidic residues (glutamic and aspartic) existed in the amide form. The first twenty N-terminal amino acids were sequenced. Some homology appeared to exist between the alpha-amylase II inhibitor and trypsin inhibitor from barley. Complex formation between alpha-amylase II and the inhibitor was detected by the appearance of a new molecular weight species after gel filtration on Bio-Gel P 100. Enzyme and inhibitor had to be preincubated for 5 min, prior to assaying for enzyme activity before maximum inhibition was attained. Inhibition increased at higher pH values. At pH 5.5, an approximately 1100 molar excess of inhibitor over alpha-amylase II produced 40% inhibition, whereas, at pH 8.0, a 1:1 molar ratio of inhibitor to enzyme produced the same degree of inhibition.

Two individuals showing features typical of the autosomal recessive Ellis-van Creveld syndrome have been diagnosed in a population of 1340 individuals living on a small island off the west coast of Scotland. Clinical features and family relationships of the affected individuals are described.

This study examined the effects of memory training on the relationship between perceived recall confidence and recall performance. The sample consisted of 76 elderly, community dwelling volunteers. Fifty-nine individuals received eight hours of memory training; the remaining 17 were wait-list controls. Participants were tested at pre- and post-intervention, and rated their confidence for recall of name-face pairs prior to each testing. The results showed a significant improvement in name-face recall at post test, favoring the group receiving mnemonic training. There was a significant association found between confidence ratings and recall performance at post-test. A closer examination of standardized regression residuals (confidence ratings and number of name-face pairs recalled) revealed that with mnemonic training, there was an improvement in the relationship between perceived confidence and recall performance following mnemonic training. The results suggest that the ability to assess changes in recall capacity and to judge future memory performance is enhanced by exposure to mnemonic training.

The present study explores the effects of age on the priming of alternate homophone spellings and recognition memory. Sixteen young and sixteen elderly adults were given a general information test, a spelling test, and a test of recognition memory. By embedding the less frequently spelled member of different homophone units (e.g., write vs. right) in the general information questions, certain of the homophones were primed during this task. The effect of this priming was assessed through the subjects' choice of spelling for these words on the spelling test. Recognition memory was assessed by asking subjects to indicate which words from a longer list were presented during the spelling test. As found in prior research priming effects were observed in younger subjects; however, no significant priming effects occurred in the older age group. On the recognition test, homophones were more often correctly recognized than nonhomophones, and priming affected the scores of the young negatively, but had no effects, positive or negative, on the elderly. These results suggest possible differences in the underlying bases of memory loss in aged adults and amnesics.

Carboxymethyl cellulose (CMC) formed insoluble complexes with beta-lactoglobulin, bovine serum albumin and Na caseinate. Maximum precipitation of the beta-lactoglobulin-CMC complex occurred at pH 3-2, whereas maximum precipitation of the bovine serum albumin. The percentage of protein precipitated by CMC decreased with increasing ionic strength of the solution, the rate of decrease being least for bovine serum albumin. At a given ionic strength, more protein was precipitated by CMC of high degree of substitution than by CMC of low degree of substitution. The change in pH (delta pH) occurring on mixing CMC and unbuffered protein solutions, each initially at the same pH, was measured. delta pH was negative for beta-lactoglobulin-CMC mixtures over the pH range 7--2 (minimum at pH 5-5). For bovine serum albumin--Cmc and Na caseinate--CMC mixtures, delta pH was positive between pH 7 and 3-2 (maximum at pH 4-5), zero at pH 3-2 and negative between pH 3-2 and 2-0 (minimum at pH 2-8).

The overnight urinary albumin excretion rate (AER) of 87 patients with insulin-dependent diabetes mellitus was measured in 1966-67, 14 years later information was obtained on 63 of the original cohort; those alive were restudied, and for those who had died relevant clinical information and case of death were recorded. The development of clinical diabetic nephropathy ('Albustix'positive proteinuria) was related to the 1966-67 AER values. Clinical proteinuria developed in only 2 of 55 patients with AER below 30 microgram/min but in 7 of 8 with AER between 30 and 140 microgram/min. The risk of clinical diabetic nephropathy in the latter group was twenty-four time higher than inthe former. 9.1% of patients with AER below 30 microgram/min had died, compared with 37.5% with higher AER. The two groups did not differ significantly in age, sex composition, and initial blood pressure. Mean duration of diabetes was longer, but not significantly so, in those with AER above 30 microgram/min. Thus, elevated levels of microalbuminuria strongly predict the development of clinical diabetic nephropathy. These levels of AER are potentially reversible, and their detection and treatment may prevent diabetic renal disease.

An endogenous alpha-amylase inhibitor was found to be synthesized in embryos of developing barley grain (Hordeum vulgare cv Bonanza). Accumulation of this protein occurred late in development (stage IV), at the same time that endogenous abscisic acid (ABA) showed a large increase. The inhibitor could be induced up to 23-fold in isolated immature embryos (stage III) by culture in ABA. Precocious germination was also blocked in stage III embryos by ABA. Dehydration stress on the isolated immature embryos also induced higher levels of the inhibitor and ABA. An even greater response to dehydration stress was observed in young seedlings, where inhibitor content increased 20-fold and ABA increased 80-fold during water stress. The high degree of correlation between ABA and inhibitor contents in in situ embryos, dehydrated embryos and young seedlings, as well as the increase in inhibitor caused by exogenously applied ABA to isolated embryos, suggests that increased alpha-amylase inhibitor synthesis in response to dehydration stress is mediated by ABA.

Heart rate, body temperature, arterial blood gas tensions, pHa and hemoglobin concentrations were measured during and after free diving of the Weddell seal (Leptonychotes weddelli), beneath the fast ice of McMurdo Sound, Antarctica. To examine arterial nitrogen tensions (PaN2), 47 samples of arterial blood were obtained from 4 seals diving up to 23 min to depths of 230 m. Peak arterial nitrogen tensions between 2000 and 2500 mmHg were recorded at depths of 40-80 m during descent, indicating that the seal's lung collapses by 25-50 m. Then arterial blood nitrogen tensions slowly decreased to about 1500 mmHg near surfacing. Thus during diving alveolar collapse and redistribution of blood nitrogen allow the seal to avoid nitrogen narcosis and decompression sickness. The arterial PO2 (PaO2) at rest (78 +/- 13 mmHg, mean +/- SD) increased with diving compression to a maximum measured value of 232 mmHg and then rapidly decreased to 25-35 mmHg. The lowest diving PaO2 was 18 mmHg just before the seal surfaced from a 27-min dive. A consistent increase of arterial hemoglobin concentrations occurred during each dive. We suggest that an extension of the sympathetic outflow of the diving reflex caused profound contraction of the Weddell seal's spleen.

All the known diabetic patients (917) from a defined population (90,660) were called for review by a single observer. A total of 842 (92%) attended and proteinuria, identified using Albustix (0.3 g/l or more), was found in 57 cases (6.8%), but in 9 this was in association with a urinary tract infection. Diastolic blood pressure, an ulcerated or amputated lower limb, and smoking category were found to be the only significant predictors of proteinuria after a multiple logistic regression analysis. A serum creatinine greater than 150 mumol/l was found in 29 (3.8%) of the 768 diabetics in whom it was measured. However, proteinuria was only present in 7 of the diabetics with impaired renal function. In those aged less than 65 years, the prevalence of proteinuria with impaired renal function was 0.75%.

Mitochondrial preparations isolated from aged white potato (Solanum tuberosum L.) slices exhibited classical cyanide-insensitive O(2) uptake which was inhibited by salicylhydroxamic acid and tetraethylthiuram disulfide (disulfiram). These mitochondria also possessed lipoxygenase activity, as determined by O(2) uptake in the presence of 4 millimolar linoleic acid. Purification of the mitochondrial preparation on a continuous Percoll gradient resulted in a large decrease in lipoxygenase activity whereas cyanide-insensitive (disulfiram sensitive) O(2) consumption was still observed. These data indicate that cyanide-insensitive O(2) consumption in mitochondrial preparations isolated from aged white potato slices is of mitochondrial origin and not due to lipoxygenase contamination.

One hundred twenty-eight elderly adults were recruited to assess the effects of affective judgment, imagery, and relaxation pretraining on mnemonic training. Participants were assigned to one of the following conditions: (1) visual imagery and affective judgment pretraining plus mnemonic training, (2) visual imagery pretraining only plus mnemonic training, (3) relaxation pretraining plus mnemonic training, (4) nonspecific pretraining plus mnemonic training, (5) nonspecific pretraining only, and (6) wait list. Subjects were tested at three times: prior to training (Time 1), following pretraining (Time 2), and at the conclusion of mnemonic training (Time 3). Although those receiving active pretraining plus mnemonics did not differ from one another at Time 3, they recalled more than those with no active pretraining. The results suggest that for mnemonics to be effective they should be coupled with active pretraining techniques.

We compared the schedules and responsibilities of medical interns at an urban university hospital in 1967 with those in 1987. We analyzed admissions, length of stay, diagnostic problems, demographic data on interns, changes in diagnostic and therapeutic options, and number and type of consultations. The intern in 1987 spent less time in the hospital but had more admissions, more interruptions, more clerical responsibilities, and more therapeutic and diagnostic options, and was more dependent on senior colleagues with special expertise. For these reasons the intern in 1987 had less time with individual patients and less autonomy than his 1967 counterpart. Recognition and modification of the negative aspects of medicine interns' experience will increase the attractiveness of internal medicine residencies.

In a study to monitor the acceptability of using a timed overnight urine collection to measure microalbuminuria in a large diabetic population, it was found that only 184 (69.4%) of 265 diabetics returned the urine collection to the hospital laboratory. Three proposals for an initial screening test to predict high risk microalbuminuria were analysed. Proposal I: a random urinary albumin concentration (RAC) greater than 25 micrograms/ml predicts an overnight albumin excretion rate (AER) greater than 30 micrograms/min. In 159 diabetics, the sensitivity of this screening test was 56%, specificity 81%, and predictive value 15%. Proposal II: an albumin concentration greater than 20 micrograms/ml in an early morning urine sample predicts an overnight AER greater than 30 micrograms/min. In 175 diabetics, the sensitivity of this screening test was 86%, specificity 97%, and predictive value 71%. Proposal III: an albumin/creatinine ratio (albumin mg/l creatinine mmol/l) greater than 3.5 in an early morning urine sample predicts an overnight AER greater than 30 micrograms/minute. In 171 diabetics, the sensitivity of this screening test was 100%, specificity 95%, and predictive value 64%. It is concluded that an albumin/creatinine ratio performed on an early morning urine sample brought to the diabetic clinic would be a useful initial screening test to detect an overnight AER greater than 30 micrograms/min.

During periods of O2 lack in liver of seals, mitochondrial respiration and adenosine triphosphate (ATP) synthesis are necessarily arrested. During such electron transfer system (ETS) arrest, the mitochondria are suspended in functionally protected states; upon resupplying O2 and adenosine diphosphate (ADP), coupled respiration and ATP synthesis can resume immediately, implying that mitochondrial electrochemical potentials required for ATP synthesis are preserved during ischemia. A similar situation occurs in the rest of the cell since ion gradients also seem to be maintained across the plasma membrane; with ion-specific channels seemingly relatively inactive, ion fluxes (e.g., K+ efflux and Ca++ influx) can be reduced, consequently reducing ATP expenditure for ion pumping. The need for making up energy shortfalls caused by ETS arrest is thus minimized, which is why anaerobic glycolysis can be held in low activity states (anaerobic ATP turnover rates being reduced in ischemia to less than 1/100 of typical normoxic rates in mammalian liver and to about 1/10 the rates expected during liver hypoperfusion in prolonged diving). As in many ectotherms, an interesting parallelism (channel arrest coupled with a proportionate metabolic arrest at the level of both glycolysis and the ETS) appears as the dominant hypoxia defense strategy in a hypoxia-tolerant mammalian organ.

Arachidonic acid is metabolized to prostaglandins and thromboxane via the cyclooxygenase pathway and to leukotrienes B4, C4, D4, and E4 via the lipooxygenase pathway. A possible role played by leukotrienes in cardiogenic shock resulting from anaphylaxis prompted us to investigate the action of these compounds on coronary vessels and myocardial contractility. In this study leukotriene B4 (LTB4) and C4 (LTC4) were injected directly into the left circumflex (LCx) coronary artery of nine anesthetized Suffolk sheep. LTB4 had no effect on coronary artery blood flow or myocardial contractility, but 3 X 10(-9) mole induced profound transient circulating neutropenia, reflecting the potent chemotactic and chemokinetic properties of this compound. Injecting as little as 1.6 X 10(-11) mole of LTC4 caused a 14.5 +/- 4.3% (mean +/- SE) reduction of LCx coronary artery flow while 1.6 X 10(-10) mole caused a 26.5 +/- 3.7% decrease of LCx coronary artery flow and an 18.1 +/- 3.2% decrease in systolic shortening of the myocardial region supplied by the LCx coronary artery. Since the decrease in systolic shortening was far greater than that expected on the basis of the reduction in coronary artery flow, we postulate that LTC4 has a direct negative inotropic effect. FPL 55712, a receptor antagonist of leukotrienes C4, D4, and E4, blocked the vasoconstriction induced by LTC4 but only partially blocked the negative inotropic effects of LTC4. LTC4 is a potent vasoconstrictor and negative inotropic agent and may play an important role in anaphylactic shock.

If the lunar surface becomes available for conducting physical experiments, it may be particularly suited to thermal neutron and molecular and atomic beam measurements. The application of these beams for the purpose of communication on the lunar surface appears possible.