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Biomedical subjects

M Manning

Publications and source records attributed to M Manning.

At least 109 records · Page 6Linked to original sources
PubMed1989

The disadvantages of dextrality for intelligence.

The right shift (RS) theory of handedness suggests that the human bias to dextrality has costs as well as benefits. Samples of children from six primary schools were individually tested for hand preference, hand skill and Raven's Matrices. Scores on standardized educational tests recently given by teachers were available for three schools. When children were stratified for ability, the distributions of hand preference and of right minus left (R-L) hand skill were as expected if extent of RS is inversely related to ability. When children were classified for R-L score, the most strongly dextral children were poorer than all others for Matrices, English and several other tests. The trend for ability to decline from left to right across the laterality continuum was consistent for all scores available. Strong dextrality is associated with weak left-hand skill, not good right-hand skill, in accord with the hypothesis that the costs of RS are to the right hemisphere. The findings and their interpretation are discussed in comparison with Geschwind's theory of developmental pathology, and for their implications for theories of hemisphere specialization.

Cerebral Cortex↗
PubMed1988

125I-d(CH2)5[Tyr(Me)2, Tyr(NH2)9]AVP: iodination and binding characteristics of a vasopressin receptor ligand.

A radioiodinated vasopressin antagonist, d(CH2)5[Tyr(NH2)9]AVP has been prepared. Iodination was carried out at the phenyl moiety of the tyrosylamide residue at position 9, followed by HPLC purification. Non-radiolabelled monoiodinated antagonist was used as a reference for identification. 125I-d(CH2)5[Tyr(Me)2, Tyr(NH2)9]AVP binding appeared to take place with a dissociation constant of 0.28 +/- 0.09 nM (Kd +/- SD) to V1 vasopressin receptors on rat liver membranes.

Animals↗
PubMed1988

125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT: a selective oxytocin receptor ligand.

An oxytocic antagonist, [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid,2-O-methyltyrosine,4-threonine, 8-ornithine,9-tyrosylamide]vasotocin (d(CH2)5[Tyr(Me)2, Thr4,Tyr-NH2(9)]OVT [corrected], was monoiodinated at the phenyl moiety of the tyrosylamide residue at position 9. 125I-labelling was performed with 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenyl-glycoluril. Iodination resulted in an increased affinity for rat uterine oxytocin receptors. A considerably lower affinity for rat vascular V1- and renal V2-receptors was found, resulting in a highly specific oxytocin receptor ligand. 125I-labelled d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT [corrected] was demonstrated to bind selectively to one population of binding sites in rat uterus and ventral hippocampal membrane preparations. Dissociation constants ranged between 0.03 and 0.06 nM. After 3 days of exposure autoradiography revealed binding in regions known to contain oxytocin receptors as well as labelling in some new regions, while no binding was found in the lateral septum, a structure containing mainly [8-arginine]vasopressin receptors. The high specific radioactivity of 125I-labelling allowed important reductions in membrane protein amount, gain in precision of binding analysis as well as considerably lower exposure times for autoradiography.

Animals↗
PubMed1988

Novel linear antagonists of the antidiuretic (V2) and vasopressor (V1) responses to vasopressin.

We report the solid phase synthesis of a series of 16 linear analogues of the cyclic antagonist of the antidiuretic (V2) and the vasopressor (V1) responses to arginine vasopressin (AVP), d(CH2)5[D-Tyr(Et)2, Val4]AVP(A). Peptide 1, the linear precursor of (A), (CH2)5(SH)-CH2-CO-D-Tyr(Et)-Phe-Val-Asn-Cys-Pro-Arg-Gly-NH2 was modified at position six with alpha-L-aminobutyric acid (Abu) to give peptide 2. Further modifications of the Abu6 analogue (No. 2) at position one by substituting cyclohexylacetic acid (Caa), cyclohexylpropionic acid (Cpa), 1-adamantaneacetic acid (Aaa), phenylacetic acid (Phaa), tert.-butylacetic acid (t-Baa), isovaleric acid (Iva), propionic acid (Pa), L-penicillamine (P), tert.-butoxycarbonyl (Boc) or omitting any substituent at this position, and/or in combination with Arg-NH2(9), Ala-NH2(9), D-Arg8-Arg-NH2(9), and desGly9 modifications yielded the remaining 14 peptides. All 16 peptides were examined for agonistic and antagonistic potencies in AVP V2 and V1 assays in rats. Apart from the Cpa analogue and the analogue lacking any substituent in the 1-position, all exhibit substantial V2 and V1 antagonism. A number are as potent as (A) as V2 antagonists. With an anti-V2 pA2 = 8.11 +/- 0.07, Aaa-D-Tyr(Et)-Phe-Val-Asn-Abu-Pro-Arg-Arg-NH2 (No. 6) is as potent as any cyclic AVP V2 antagonist reported to date. The PaI analogue of No. 6 exhibits promising anti-V2/anti-V1 selectivity. These findings prove conclusively that a ring structure is not a requirement for recognition of or for binding to AVP V2 or V1 receptors. This discovery thus offers a promising new approach to the design of peptide and non-peptide antagonists of AVP and perhaps also to other cyclic peptides such as somatostatin, atrial-natriuretic factor, insulin, and the recently discovered endothelin. Some of these linear antagonists may be of value as pharmacological tools and as therapeutic agents.

Amino Acid Sequence↗
PubMed1988

Strategic pricing: hitting the mark with pricing strategies. Part 1.

Efforts by government and business to reduce healthcare expenditures by fostering competition and reducing utilization have combined to redefine the basic economic structure of the healthcare delivery system. Increased competition among providers has prompted an increased awareness of strategic pricing as a means of achieving institutional goals and objectives. In this article, the first in a three-part series on strategic pricing, the authors examine some of the key theoretical considerations related to pricing strategies for healthcare providers. Future articles will examine practical applications as they relate to package pricing, discounting, per diem systems, and capitation arrangements.

Economic Competition↗
PubMed1988

Discounting and per diem arrangements lock in patient referrals. Part 2.

Discounting and per diem arrangements are the most popular payment methods used by hospitals today because they are relatively simple methods. A properly negotiated discount or per diem contract can provide a hospital with the opportunity to lock in patient referrals from the many healthcare providers in its local markets. This article is the second in a three-part series on the strategic pricing of healthcare services. The final article discusses the intricacies of capitation arrangements, an increasingly popular payment method for healthcare services.

Contract Services↗
PubMed1987

Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization.

Gram-negative nosocomial pneumonia may result from retrograde colonization of the pharynx from the stomach, and this may be more likely when the gastric pH is relatively high. We studied the rate of nosocomial pneumonia among 130 patients given mechanical ventilation in an intensive care unit who were receiving as prophylaxis for stress ulcer either sucralfate (n = 61), which does not raise gastric pH, or conventional treatment with antacids, histamine type 2 (H2) blockers, or both (n = 69). At the time of randomization to treatment, the two groups were similar in age, underlying diseases, and severity of acute illness. Patients in the sucralfate group had a higher proportion of gastric aspirates with a pH less than or equal to 4 (P less than 0.001) and significantly lower concentrations of gram-negative bacilli (P less than 0.05) in gastric aspirates, pharyngeal swabs, and tracheal aspirates than did patients in the antacid-H2-blocker group. The rate of pneumonia was twice as high in the antacid-H2 group as in the sucralfate group (95 percent confidence interval, 0.89 to 4.58; P = 0.11). Gram-negative bacilli were isolated more frequently from the tracheal aspirates of patients with pneumonia who were receiving antacids or H2 blockers. Mortality rates were 1.6 times higher in the antacid-H2 group than in the sucralfate group (95 percent confidence interval, 0.99 to 2.50; P = 0.07). Although our results fell just short of statistical significance when they were analyzed according to intention to treat, they suggest that agents that elevate gastric pH increase the risk of nosocomial pneumonia in patients receiving ventilation by favoring gastric colonization with gram-negative bacilli. We conclude that in patients receiving mechanical ventilation, the use of a prophylactic agent against stress-ulcer bleeding that preserves the natural gastric acid barrier against bacterial overgrowth may be preferable to antacids and H2 blockers.

Antacids↗
PubMed1987

Bacterial colonization in humidifying cascade reservoirs after 24 and 48 hours of continuous mechanical ventilation.

We evaluated levels of bacterial colonization in the humidifying cascade reservoirs of 466 mechanical ventilators; 326 reservoirs were cultured after 24 hours and 140 were cultured after 48 hours of continuous mechanical ventilation. Bacterial colonization was absent in 284 (87.1%) of the humidifier reservoirs sampled at 24 hours and 125 (89.3%) of the reservoirs cultured at 48 hours. Levels of bacterial colonization in the remaining humidifiers were low (less than 100 organisms/mL). The median temperature recorded in the reservoir fluid of 30 different ventilators was 50 degrees C (range 40 degrees to 60 degrees C). In vitro seeding of reservoir fluid at 50 degrees C with 10(6) organisms/mL of four different species of nosocomial gram-negative bacilli and Staphylococcus aureus demonstrated rapid killing of all five strains over a 6-hour incubation period, and no significant bacterial aerosols were detected. Rates and levels of bacteria in heated humidifier reservoirs are low and nosocomial pathogens survive poorly at the median reservoir temperature of 50 degrees C. We conclude that the heated humidifier reservoir on a mechanical ventilator is an unlikely source of colonization or bacterial aerosols, and therefore it can be changed every 48 hours with the ventilator tubing.

Bacteria↗
PubMed1987

C-terminal deletions in agonistic and antagonistic analogues of vasopressin that improve their specificities for antidiuretic (V2) and vasopressor (V1) receptors.

We report the solid-phase synthesis of 12 desGly and 12 desGly(NH2) analogues of arginine-vasopressin (AVP), two highly selective antidiuretic (V2) agonists, four vasopressor (V1) antagonists, and five V2/V1 antagonists. The parent AVP agonists are (1) AVP, (2) 1-deamino[8-D-arginine]vasopressin (dDAVP), and (3) its 4-valine analogue, dVDAVP. The parent V1 antagonists are (4) [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid)] arginine-vasopressin (d(CH2)5AVP), (5) d(CH2)5VDAVP, (6) [1-deaminopenicillamine,4-valine,8-D-arginine]vasopressin (dPVDAVP), and (7) d(CH2)5[Tyr(Me)]AVP. The parent V2/V1 antagonists are (8) d(CH2)5[D-Phe2,Ile4]AVP, (9) d(CH2)5[D-Phe2]VAVP, (10) d(CH2)5[D-Tyr(Et)2]VAVP, (11) d(CH2)5[Tyr(Et2]VAVP, and (12) d(CH2)5[D-Ile2,Ile4]AVP. All 24 analogues were tested for agonistic and antagonistic activities in in vivo rat vasopressor and rat antidiuretic assays. The desGly and desGly(NH2) analogues of 1-3 are either weak partial agonists or weak antagonists of the V1 responses to AVP. Except for desGly(NH2)AVP, which is a weak V2 agonist, the remaining desGly and desGly(NH2) analogues of 1-3 exhibit substantial V2 agonism and are thus highly selective V2 agonists. With antidiuretic activity of 321 units/mg, a resynthesized desGly(NH2)dVDAVP is equipotent with AVP as a V2 agonist. Thus our previously stated conclusion about the need for C-terminal CONH2 for V2 agonism is no longer valid. The four pairs of desGly/desGly(NH2) analogues of the V1 antagonists (4-7) all retained varying degrees of V1 antagonism and some exhibited striking enhancements in anti-V1/V2 selectivity. Thus the desGly/desGly(NH2) analogues of d(CH2)5Tyr(Me)AVP are highly potent V1 antagonists/weak V2 antagonists with anti-V1/V2 selectivities of 200 and 1200, respectively. The four pairs of desGly/desGly(NH2) analogues of the V2/V1 antagonists (8-11) exhibited enhancements, full retention, or slight diminishment of both V1 and V2 antagonism, with the desGly analogue being usually the more potent of each pair. The desGly and desGly(NH2) analogues of d(CH2)5[D-Ile2,Ile4]AVP (12) exhibited anti-V2/V1 selectivities of 46 and about 440, respectively. These are the most selective V2 antagonists reported to date. Many of these analogues could serve as useful pharmacological tools in studies on the roles of AVP in normal and pathophysiological circumstances.

Animals↗
PubMed1987

Iodination of vasopressin analogues with agonistic and antagonistic properties: effects on biological properties and affinity for vascular and renal vasopressin receptors.

Twelve L- and D-tyrosine-containing vasopressin analogues were prepared in their mono- and diiodinated forms. These include six arginine vasopressin (AVP) vascular (V1) type antagonists/antidiuretic (V2) agonists, four V1/V2 antagonists, and two V1/V2 agonists, one of which is AVP itself. Ten peptides were iodinated on the tyrosyl residue in position 2; two were iodinated on a tyrosyl amide residue replacing the glycyl amide residue at position 9. All peptides were tested both for their biological activities in vivo (rat vasopressor and antidiuretic tests) and for their ability to bind to vasopressin receptors of the V1 (vascular) and V2 (renal) types from rat liver and rat kidney membranes, respectively. It is shown that monoiodination of the tyrosyl residue in the vasopressin analogues that were tested either preserves or reduces to a highly variable extent the in vivo and in vitro biological activities of these analogues. In most cases diiodonitation resulted in a marked decrease in biological activity. The effects of iodination on the affinity of vasopressin analogues for hepatic V1 receptors and renal V2 receptors were more related to the affinity of the noniodinated peptide for these receptors than to the biological properties (antagonist versus agonist) of the tested analogues, the nature (L versus D) of the iodinated tyrosyl residue, or the position (2 versus 9) at which this residue was introduced. The loss of affinity due to iodination was usually more pronounced for peptides exhibiting high affinity for vasopressin receptors. However, we show that among the monoiodinated peptides some (especially monoiodinated [2-D-Tyrosine]-AVP) retained enough affinity for vasopressin binding sites to suggest that their radioiodinated conterparts would be promising labeled ligands for use in studies in vasopressin receptors.

Animals↗
PubMed1986

Multiple unusual manifestations of Wegener's granulomatosis: breast mass, microangiopathic hemolytic anemia, consumptive coagulopathy, and low erythrocyte sedimentation rate.

We describe a patient who presented with multiple unusual manifestations of Wegener's granulomatosis, including a breast mass, microangiopathic hemolytic anemia, and consumptive coagulopathy. Erythrocyte sedimentation rate (Westergren), usually elevated in the course of this disease, persistently remained low in this patient. We found that C-reactive protein levels were, in this case, a more sensitive gauge of disease activity.

Anemia, Hemolytic↗
PubMed1986

Synthesis and receptor specificities of vasopressin antagonists.

We present some highlights of our findings on the design and synthesis of antagonists of the vascular (V1) and renal tubular (V2) responses to arginine vasopressin. The most potent of our original V1 antagonists, [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid) 2-O-methyltyrosine] arginine vasopressin [d(CH2)5Tyr(Me)AVP], and the most potent of our original V2/V1 antagonists, [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-O-ethyltyrosine, 4-valine] arginine vasopressin [d(CH2)5Tyr(Et)VAVP], have been modified at positions 1, 2, 4, and 8 and at positions 2, 4, 7, 8, and 9, respectively. A number of highly potent and highly selective arginine vasopressin (AVP) V1 and AVP V2/V1 antagonists have resulted from these studies. The in vivo antioxytocic properties of many of those antagonists are also given here, a number for the first time. We also present preliminary data on some orally active antagonists. A number of these antagonists have become valuable pharmacological tools in studies on the physiological and pathophysiological roles of AVP. In addition, the AVP V2 antagonists may be of therapeutic value for the treatment of hyponatremia resulting from the excessive secretion of AVP.

Animals↗
PubMed1986

Vasopressin antagonists allow demonstration of a novel type of vasopressin receptor in the rat adenohypophysis.

The ligand specificity of rat adenohypophyseal vasopressin receptors was directly compared to that of peripheral receptors of the V1 and V2 types. For this purpose a series of 15 recently designed vasopressin antagonists was used. The affinities of these antagonists for rat adenohypophyseal membranes were deduced from the determination of the concentration-dependent inhibition of [3H]vasopressin binding. In parallel experiments the corticotropin (or anti-corticotropin)-releasing activities of the tested peptides were determined on freshly dispersed rat adenohypophyseal cells. All peptides tested which were found to be antagonists of the vasopressor and antidiuretic responses to vasopressin in vivo behaved as antagonists of vasopressin-induced corticotropin release. There was a close correlation between the relative affinities of the analogues tested for binding to adenohypophyseal membranes and their relative potencies in inhibiting vasopressin-induced corticotropin release, indicating that the detected vasopressin-binding sites are the receptors involved in the vasopressin effect on corticotropin secretion. No correlation could be demonstrated between anti-corticotropin-releasing activities and either anti-antidiuretic or antivasopressor potencies of the antagonists tested. A direct comparison of the ligand specificities of adenohypophyseal receptors on the one hand, and V1 (hepatic) and V2 (renal) receptors on the other hand, showed that most of the antagonists discriminated very efficiently between adenohypophyseal and either hepatic or renal receptors. The selectivity index reaches values as high as 260,000 for desGly(NH2)9 [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-D-O-ethyl-tyrosine, 4-valine] arginine vasopressin. It is concluded that adenohypophyseal receptors represent a novel type of vasopressin receptors. Based on the observation that adenohypophyseal receptors, like hepatic or vascular V1 receptors, do not appear to be coupled to adenylate cyclase, we propose that adenohypophyseal receptors could be designated as V1b receptors as opposed to the V1a receptors previously characterized on liver and blood vessels.

Adrenocorticotropic Hormone↗
PubMed1985

Effects of phencyclidine on active avoidance and escape in rats.

Rats trained to avoid electrical shock in a shuttle box were given phencyclidine (0.0, 1.0, 5.0, or 10.0 mg/kg) prior to testing for 5 consecutive days. There was a dose-dependent increase in both avoidance and escape failures although animals continued to cross the barrier during intertrial intervals, indicating that they were capable of making the appropriate response. Little evidence of tolerance was found during the 5-day testing period.

Animals↗