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Biomedical subjects

G E Murphy

Publications and source records attributed to G E Murphy.

At least 19 recordsLinked to original sources

Long-range interactions in the dimer interface of ornithine decarboxylase are important for enzyme function.

Ornithine decarboxylase (ODC) is a pyridoxal 5'-phosphate dependent enzyme that catalyzes the first committed step in the biosynthesis of polyamines. ODC is a proven drug target for the treatment of African sleeping sickness. The enzyme is an obligate homodimer, and the two identical active sites are formed at the dimer interface. Alanine scanning mutagenesis of dimer interface residues in Trypanosoma brucei ODC was undertaken to determine the energetic contribution of these residues to subunit association. Twenty-three mutant enzymes were analyzed by analytical ultracentrifugation, and none of the mutations were found to cause a greater than 1 kcal/mol decrease in dimer stability. These data suggest that the energetics of the interaction may be distributed across the interface. Most significantly, many of the mutations had large effects (DeltaDeltaG kcat/Km > 2.5 kcal/mol) on the catalytic efficiency of the enzyme. Residues that affected activity included those in or near the substrate binding site but also a number of residues that are distant (15-20 A) from this site. These data provide evidence that long-range energetic coupling of interface residues to the active site is essential for enzyme function, even though structural changes upon ligand binding to wild-type ODC are limited to local conformational changes in the active site. The ODC dimer interface appears to be optimized for catalytic function and not for dimer stability. Thus, small molecules directed to the ODC interfaces could impact biological function without having to overcome the difficult energetic barrier of dissociating the interacting partners.

Alanine↗

Cognitive behavior therapy, relaxation training, and tricyclic antidepressant medication in the treatment of depression.

Outcomes of seven treatment trials comparing cognitive behavioral therapy to treatment with tricyclic antidepressant medication in major depressive disorder have been quite similar to one another. This led us to question whether treatment outcome in time-limited studies reflected a unique effect of cognitive behavioral therapy. To test the uniqueness hypothesis, relaxation training, a nonpharmacologic, noncognitive treatment, was chosen as a comparison for cognitive behavioral therapy as well as drug therapy. Treatment duration was 16 weeks. The sample of 37 patients treated for major depressive disorder was less depressed than those previously studied. For both cognitive behavioral therapy and relaxation training, outcome of depression was superior to that of tricyclic antidepressant medication by endpoint analysis. The posttreatment scores on the Beck Depression Inventory of 82% of the group receiving cognitive behavioral therapy improved to a Beck Depression Inventory score < or = 9 which was not significantly greater than that for the group receiving relaxation training (73%), so a unique effect was not demonstrated for cognitive behavioral therapy. The outcome for tricyclic antidepressant medication (29% improved to criteria) was significantly worse than that for cognitive behavioral therapy. The patient's pretreatment initial expectancy was not predictive.

Adolescent↗

39 years of suicide research: a personal view.

This is a personal account of the beginning of clinical research in suicide in a hostile intellectual climate, of the methodology that has informed most of the subsequent research, and of the very durable findings of that work over 12 replications. The genius of the late Dr. Eli Robins lies at the base, not only of this research methodology, but of the diagnostic system that gives it clinical meaning. All of this is now commonplace, but it was not always so.

History, 20th Century↗

Comparison of efficacy of longest, average, and shortest axial length measurements with a solid-tip ultrasound probe in predicting intraocular lens power.

The accuracy of intraocular lens power predictions was calculated for 93 eyes using the shortest, average, and longest of multiple solid-tip probe ultrasound axial length readings for each eye. Averaging the readings reduced the effect of corneal indentation. The single longest and average readings gave comparable results.

Anthropometry↗

Effects of various supplements on voluntary intake and performance by growing cattle consuming forage moderate to high in crude protein.

Growing cattle were supplemented with substances to lessen or increase ruminal ammonia level to determine if consumption of moderate- to high-crude protein (CP) forage is limited by high ruminal ammonia absorption. In Experiment 1 (5 x 5 Latin square), five Holstein steers (198 kg) had ad libitum access to alfalfa cubes (17% CP) without supplementation or with corn at 0.25 or 0.75% body weight (BW) alone (LC or HC) or with 0.06% BW of zeolite (chabazite; LC-Z and HC-Z). Total daily organic water (OM) intake was not affected by treatment (6.08, 6.14, 6.11, 6.19 and 6.09 kg for control, LC, LC-Z, HC and HC-Z, respectively; SE 0.25). In Experiment 2, Simmental crossbred beef calves grazed fescue-clover paddocks in the spring (clipped forage: 21 to 27% CP) for 84 days and were supplemented with 0.25 or 0.75% BW corn alone or with added zeolite (0.06% BW) or lasalocid (0.5 mg/kg BW). Daily gain did not differ among treatments (1.24 to 1.31 kg/day). In Experiment 3 (6 x 6 Latin square), six Holstein steer calves (168 kg) had ad libitum access to medium-quality, orchardgrass-clover hay (15% CP). Steers received one of the following six treatments: no supplement (Control), 0.35% BW ground corn (C), corn plus 0.049% BW urea (C-U), 0.35% BW soybean meal (S), 0.205% BW feather meal (F) or 0.103% BW feather meal, 0.052% BW blood meal and 0.067% BW corn gluten meal (F-BG). Total daily OM intake was 5.00, 5.14, 5.00, 5.11, 4.84 and 4.70 kg for control, C, C-U, S, F and F-BG, respectively (SE 0.13). In Experiment 4 (6 x 6 Latin square), six Holstein steer calves (226 kg) were fed 0.75% BW of alfalfa cubes (19% CP) plus ad libitum access to medium- to high-quality orchardgrass hay (16% CP). Steers received one of the following six treatments: no supplement (Control), corn at 0.25% BW alone (c) or mixed with 0.12% BW peanut skins (C-PSK), a mix of high-CP feedstuffs high in ruminal escape protein (0.029% BW blood meal, 0.038% BW corn gluten meal and 0.028% BW feather meal; C-REP), 0.139% soybean meal (C-S) or soybean meal plus peanut skins (C-PSK-S). Total daily OM intake was 6.16, 6.25, 6.13, 6.52, 6.50 and 6.60 kg for control, C, C-PSK, C-REP, C-S and C-PSK-S, respectively (SE 0.10).(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

Multiple risk factors predict suicide in alcoholism.

From a study of the lives of 50 alcoholics who committed suicide, seven nonacute clinical/historical features were identified post hoc that appear to be intimately linked to suicide. They included continued drinking, major depressive episode, suicidal communication, poor social support, serious medical illness, unemployment, and living alone. This study examined whether these features are common to alcoholics generally and/or to nonalcoholics who commit suicide or if they may be specifically predictive of suicide in alcoholics. The frequencies of these factors were compared with those in an earlier sample of 32 alcoholics who committed suicide, then with data from two St Louis studies of living alcoholics and a cohort of individuals with major depressive disorder who committed suicide. The frequency of the identified items was replicated among the 32 alcoholics in a larger community sample of individuals who committed suicide. The white men from those two samples of alcoholics who committed suicide were then combined for the advantage of sample size. Six of the seven factors could be compared with a population survey sample of 106 living alcoholics and five with a clinically identified sample of 142 living alcoholics. All compared factors were significantly more frequent among those who committed suicide than among controls. Any four of the six factors identified 46 (69%) of the 67 individuals who committed suicide with few false-positive results among the controls. Regarding all seven of the identified factors, 54 (81%) of the 67 men and 64 (83%) of the entire sample of 82 individuals who committed suicide had four or more risk factors. Alcoholic women and blacks showed the same pattern as white men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Minimizing anisometropia in bilateral pseudophakia.

One hundred twenty patients who had bilateral posterior chamber intraocular lens implantation were analyzed for postoperative anisometropia. All pairs of lenses had the same A constant and similar designs. Several parameters were analyzed to identify patients at higher risk for clinically significant anisometropia upon implantation of the second eye and determine whether the results of the first eye could be used to modify the implant power selected for the second eye to reduce the risk of anisometropia. In most cases, simply using the value of the linear regression prediction for emmetropia in the second eye without modifications minimized anisometropia.

Anisometropia↗

Prescribing therapy for depression: the role of learned resourcefulness, a failure to replicate.

Work in 1985 by Simons, Lustman, Wetzel, and Murphy showed that a patient's score on Rosenbaum's self-control scale predicted differential response to treatments for depression, with a high score predicting a good outcome with talking therapy and a low score a good outcome with drug therapy. This study of 37 patients did not replicate those findings. Using the same paradigm, we predicted response correctly 7 times and incorrectly 16 times, a clear failure. A valid method for choosing the best treatment for a patient with major depression remains to be found.

Adult↗

Digestion, feed intake, and live weight gain by cattle consuming bermudagrass hay supplemented with whey.

Three experiments were conducted with cattle consuming bermudagrass hay to determine whether low-level supplements of whey alone, corn alone, or whey plus corn affect feed intake, digestion, and(or) BW gain. Six ruminally and duodenally cannulated beef cows (574 kg), used in a Latin-square trial (Exp. 1), were fed bermudagrass hay without supplementation (control) or with 2.8% whey (low whey, LW), 5.6% whey (high whey, HW), 17.4% ground corn (C), 2.8% whey plus 14.9% corn (C-LW), or 5.6% whey plus 12.4% corn (C-HW). Supplementing with whey and(or) corn increased ruminal butyrate (8.8, 9.4, 10.0, 9.6, 10.5, and 11.0 mol/100 mol of total VFA for control, LW, HW, C, C-LW, and C-HW, respectively; SE = .20). Supplements did not affect microbial N flow at the duodenum. Six Holstein steer calves (158 kg) in a Latin square (Exp. 2) consumed bermudagrass hay ad libitum alone (control) or with .075 or .15% BW whey (LW and HW, respectively), .5% BW ground corn (C), or corn-whey mixes made by substituting whey for corn (C-LW and C-HW). Substituting .15% BW of whey for corn increased (P less than .05) total OM intake slightly (3.99, 3.84, 3.75, 4.11, 4.28, and 4.47 kg for control, LW, HW, C, C-LW, and C-HW, respectively; SE = .10). In an 84-d randomized block experiment (Exp. 3), 96 beef calves (194 kg) consumed (ad libitum) low-quality bermudagrass hay alone or with C, LW, HW, C-LW, or C-HW supplements.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Effects of animal and supplement characteristics on average daily gain of grazing beef cattle.

Effects of animal gender and age, use of a growth stimulant, and supplementation with grain alone or grain plus other substances on ADG by growing beef cattle grazing bermudagrass paddocks with sod-seeded rye, wheat, and ryegrass were determined. Two grazing experiments (Exp. 1: late winter through mid-spring; Exp. 2: late spring through mid-summer) were conducted. Experiment 1 used 96, 12- to 13-mo-old Simmental-cross calves (heifers, 240 kg; steers, 272 kg), half of which were implanted with zeranol. Within each implant treatment, cattle received no supplement or .5% BW (DM) of ground corn alone or plus a mix of protein meals, zinc sulfate, thiamin-HCl, or salt. Daily gain was higher (P less than .05) with than without supplementation and was similar (P greater than .10) among supplement treatments. In Exp. 2, 96 crossbred beef steers, approximately 7 (230 kg) or 15 mo old (250 kg), were not supplemented (control) or received .5% BW (DM) of ground corn on d 1 to 84 (C-C), corn plus a protein meal mix on d 1 to 84 (CP-CP), corn on d 43 to 84 (O-C), corn plus the protein meal mix on d 43 to 84 (O-CP), or corn on d 1 to 42 and corn plus the protein meal mix on d 43 to 84 (C-CP). Daily gain on d 1 to 84 was affected (P less than .05) by supplement, age, implant, and the supplement x implant interaction (nonimplanted: .37, .56, .68, .40, .49, and .49; implanted: .37, .62, .54, .49, .70, and .71 kg for control, C-C, CP-CP, O-C, O-CP, and C-CP, respectively).

Adipose Tissue↗

The lifetime risk of suicide in alcoholism.

Current estimates of the lifetime risk of suicide in alcoholism (11% to 15%) are shown statistically to be untenable. Examination of the mortality from suicide in all published follow-up studies of alcoholics containing the requisite data permits calculation of a much smaller lifetime suicide risk: about 2% in untreated and 2.21% in outpatient-treated probands. Studies of alcoholics identified from hospital admissions yield a lifetime risk of about 3.4% for the United States, the United Kingdom, and other English-speaking countries. It is higher in the Scandinavian and European countries with high suicide rates, but not in those with low national suicide rates. The population at risk is shown to be about half of that commonly estimated, and consists of seriously affected alcoholics. While the annual incidence of suicide in the United States is about 1.3% currently, only that quarter of the population identifiably psychiatrically ill is at significant risk. Despite the seemingly miniscule lifetime risk of 2% to 3.4%, the likelihood of suicide in conservatively diagnosed alcoholism is between 60 and 120 times that of the non-psychiatrically ill. Such alcoholism contributes about 25% of the suicides.

Alcoholism↗

Comparison of adinazolam, amitriptyline, and placebo in the treatment of melancholic depression.

Adinazolam, a triazolobenzodiazepine, was compared with amitriptyline and placebo in a double-blind protocol involving melancholic depressives. Forty-eight patients entered the study, and 35 completed 6 weeks of evaluation. Patients were well matched in each of the groups. Initially, the adinazolam group showed more improvement than the placebo group, but this trend did not persist beyond day 7. The amitriptyline group tended to show more improvement than either the placebo or adinazolam groups, and final scores were significantly better for amitriptyline. Depressive symptoms in the amitriptyline dropout group appeared improved, whereas in the adinazolam and placebo dropout groups they were unchanged or worse. Both amitriptyline and adinazolam were more frequently associated with complaints of side effects than placebo. Thus, amitriptyline was observed to be superior to adinazolam and placebo in improvement in depressive symptoms while adinazolam had only a brief early advantage over placebo.

Adolescent↗

The changing relationship between age and suicide rates: cohort effect, period effect or both?

Massive changes in suicide rates over time have been recognized in the United States. An attempt has been made to describe these changes with age-period-cohort analyses. A variety of approaches has led us to conclude that suicide rates of non-white males, white and non-white females can be described adequately without a cohort effect. Recent suicide trends lead to the conclusion that a model based on a rising rate in more recently born white male cohorts coupled with an independent age effect could be rejected. If a cohort effect is postulated for more recent birth cohorts, it would require that the cohort suicide rate is decreasing with each successive birth cohort. Models based on high suicide rates in recent cohorts and additive age effects are probably misleading for future predictions. An association was noted between recent changes in the teenage and young adult suicide rates and rates of depression. Both may be the product of similar social influences.

Adolescent↗

Cognitive therapy and pharmacotherapy for depression. Sustained improvement over one year.

Seventy patients with nonbipolar affective disorder who completed a 12-week course of either cognitive therapy (CT), pharmacotherapy, CT plus active placebo, or CT plus pharmacotherapy were assessed one month, six months, and one year after termination of active treatment. Of the 44 patients who had originally responded to treatment, 16 relapsed as defined by reentry into treatment or by self-reported depression scores in the moderately depressed range. Twenty-eight patients remained well during the one-year follow-up. Patients with relatively high levels of remaining depressive symptoms on completion of treatment relapsed more often than those who had little or no residual depression. Further, at treatment termination, patients who relapsed had significantly higher scores on a measure of dysfunctional attitudes. Patients who had received CT (with or without tricyclic antidepressants) were less likely to relapse in the one-year follow-up period than patients who received pharmacotherapy.

Adolescent↗

A BASIC program for deriving linear regression formulas for intraocular lens power prediction.

We present an original BASIC program written specifically for the ophthalmologist that allows calculation of linear regression formulas for prediction of emmetropic lens power from the surgeon's own data. The program features ongoing data storage, options for analyzing specific ranges (such as longer axial lengths), and calculation of residuals. The program is user-friendly and may be used with minimal computer knowledge. The authors will copy the program at no charge on a user's initialized diskette.

Computers↗