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P Cunningham

Publications and source records attributed to P Cunningham.

At least 73 records · Page 4Linked to original sources
PubMed1995

The utility of the CCK DISIDA scan in the treatment of occult biliary tract disease.

The vast majority of biliary tract disease is correlated with calculi, and the diagnosis of biliary disease is made simpler when calculi are detected. There are good screening studies for the detection of calculi; however, a reproducible objective test for biliary tract disease in the absence of gallstones has been lacking. Occult biliary tract disease should be considered when symptoms typical of biliary tract disease are present, gallstones cannot be demonstrated, and other diseases have been ruled out. This is characteristically a diagnosis of exclusion, with only the subjective criteria of pain relief to validate surgical intervention. Recently, we have used a nuclear medicine test that simulates the gallbladder response to normal postprandial physiologic stress, to study in an objective fashion the gallbladder function of a group of patients who have symptoms typical of biliary tract disease, but no demonstrable calculi. We have found that the CCK DISIDA study has correlated well with occult pathology. The experience at Easton Hospital has confirmed that the CCK augmented DISIDA scan with calculation of ejection fraction is a reasonably accurate study, with a sensitivity of 88% in detecting previously suspected but undemonstrable pathology in this selected population. This corresponds closely to the observed finding that the pathology reports of 77% of the resected gallbladders noted some abnormality. Of further interest is the long term symptomatic relief achieved in 85% of the patients available for follow up interviews, including a symptomatic benefit in eight of the 11 patients with a normal pathology report.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Microsatellite DNA variation within and among European cattle breeds.

Microsatellite markers offer great potential for genetic comparisons within and between populations. We report the analysis of 12 microsatellite loci in six breeds of European cattle. This yielded a wide spectrum of variability with observed heterozygosities ranging from 0.00 to 0.91. Deviations from Hardy-Weinberg equilibrium were noted for some locus-population combinations, particularly at a microsatellite located within the prolactin gene. Also, significant linkage disequilibrium was detected between two microsatellite loci located within the bovine major histocompatibility complex, and this association was maintained across breeds, providing evidence for marker stability during short-term evolution. The mode of mutation was investigated by comparing the observed data with that expected under the infinite alleles model of neutral mutation, and six of the microsatellite loci were found to deviate significantly, suggesting that a stepwise mutation model may be more appropriate. One indication of marker utility is that, when genetic distance estimates were computed, the resultant dendrogram showed concordance with known breed histories.

Alleles↗
PubMed1994

Evidence for two independent domestications of cattle.

The origin and taxonomic status of domesticated cattle are controversial. Zebu and taurine breeds are differentiated primarily by the presence or absence of a hump and have been recognized as separate species (Bos indicus and Bos taurus). However, the most widely held view is that both types of cattle derive from a single domestication event 8000-10,000 years ago. We have examined mtDNA sequences from representatives of six European (taurine) breeds, three Indian (zebu) breeds, and four African (three zebu, one taurine) breeds. Similar levels of average sequence divergence were observed among animals within each of the major continental groups: 0.41% (European), 0.38% (African), and 0.42% (Indian). However, the sequences fell into two very distinct geographic lineages that do not correspond with the taurine-zebu dichotomy: all European and African breeds are in one lineage, and all Indian breeds are in the other. There was little indication of breed clustering within either lineage. Application of a molecular clock suggests that the two major mtDNA clades diverged at least 200,000, and possibly as much as 1 million, years ago. This relatively large divergence is interpreted most simply as evidence for two separate domestication events, presumably of different subspecies of the aurochs, Bos primigenius. The clustering of all African zebu mtDNA sequences within the taurine lineage is attributed to ancestral crossbreeding with the earlier B. taurus inhabitants of the continent.

Africa↗
PubMed1994

Psychosocial correlates of fire disaster among children and adolescents.

This study examined the extent of children's and adolescents' psychosocial maladjustment associated with a natural disaster, namely, wildfire. The course of psychopathology was assessed six weeks after a major wildfire destroyed 420 homes. Victims' functioning relative to a comparison group from the same community, matched for age, gender, socioeconomic status, and fire insurance was examined. The major goal of this study was to assess systematically the short-term mental health consequences of a wildfire disaster among children and adolescents. This goal was achieved through the use of standardized assessment procedures. The results of this study add useful information to the literature concerning the impact of disaster among children and adolescents and provide a methodological framework for future efforts in this area.

Adolescent↗
PubMed1994

American College of Surgeons trauma quality indicators: an analysis of outcome in a statewide trauma registry.

Quality assurance/quality improvement (QA-QI) is a priority for maintaining the highest standards of care in trauma systems. To be an effective tool for system review, the QA-QI indicators should identify patients with higher rates of morbidity and mortality from injury. While the American College of Surgeons (ACS) and the Joint Commission on Accreditation of Health Care Operations have identified certain audit filters within the trauma system, there are few data to substantiate the value of these audit filters for trauma care. The purpose of this study was to analyze the ability of the ACS trauma indicators to predict adverse patient outcome following injury requiring review. The study population consisted of 44,019 patients from the North Carolina State Trauma Registry from 1987 to 1992. Of the 22 audit filters nine were available for analysis. Mortality rate, length of stay, and total charges were used as measures of outcome. The hypotheses tested were that patients who met the indicator criteria would have higher mortality rates and worse outcomes than the non-indicator group. Student's t test and Chi-square analysis were used to test the differences between the group which met the criteria for the indicator and those without. Of the nine audit filters tested, only three were found to have significantly worse outcomes than their non-indicator comparison group: gunshot wound to the abdomen with non-surgical management, femur fracture without fixation, and complications from pulmonary embolism-deep vein thrombosis-decubitus ulcer (p < 0.05). Contrary to expectations, four of the audit filters, coma without intubation, laparotomy > 2 hours, transfer > 6 hours, and admission to non-surgical service, actually had significantly better outcomes than their non-indicator counterpart. Scene time > 20 minutes, laparotomy > 2 hours after arrival, and craniotomy > 4 hours after arrival may be indicators of patients at risk for morbidity. This study demonstrates that several ACS clinical indicators, as currently written, are not useful in identifying patients at higher risk for poor outcome. The indicators need further definition to be of value in the quality review process. Specifically, the study suggests that audit filters should be data driven and based upon analyses of large populations of injured patients and their outcomes to be valid QA-QI tools.

General Surgery↗
PubMed1994

Efficacy and specificity of L-692,429, a novel nonpeptidyl growth hormone secretagogue, in beagles.

L-692,429 is a substituted benzolactam that has recently been shown to stimulate GH secretion from rat pituitary cells in vitro with an ED50 of 60 nM. In the current studies, we evaluated the efficacy and specificity of L-692,429 as a GH secretagogue in beagles. L-692,429 at 0.1, 0.25, or 1.0 mg/kg or saline vehicle was administered iv to four male and four female beagles in a balanced cross-over design. Blood samples were collected up to 75 min posttreatment, and serum was assayed for GH, cortisol, PRL, and LH. Mean peak serum GH levels were significantly increased (P < 0.05) by L-692,429 to 13 +/- 2 (mean +/- SEM) ng/ml (0.1 mg/kg), 39 +/- 6 ng/ml (0.25 mg/kg), or 71 +/- 11 ng/ml (1.0 mg/kg) over the saline control value of 3.6 +/- 0.6 ng/ml. Mean peak GH levels occurred at 15 min and had returned to near-baseline levels by 75 min. There was no difference in response between sexes. Mean peak cortisol levels were significantly increased (P < 0.05) by 2.2-, 2.7-, and 3.1-fold above control levels (3.0 +/- 0.2 micrograms/dl) at 25-35 min and returned to near-baseline levels by 75 min. PRL was slightly decreased after L-692,429 treatment, whereas LH was not affected. In a second study, three groups of three male beagles each were administered 5.0 mg/kg L-692,429, iv; iv saline, or 2.2 U/kg ACTH, im. Blood was collected for 8 h posttreatment and assayed for GH, cortisol, ACTH, aldosterone, PRL, insulin, T3, and T4. L-692,429 administration significantly increased (P < 0.05) GH over the control level (6.0 +/- 3.6 ng/ml) to 133 +/- 14 ng/ml by 15 min, with a return to pretreatment levels by 120 min. Cortisol levels were significantly increased (P < 0.05) by 2.0-fold (L-692,429) or 2.9-fold (ACTH) over the saline control peak concentration of 5.6 +/- 1.6 micrograms/dl and were associated with concurrent increases in ACTH levels of 1.2-fold (L-692,429) or 2.1-fold (ACTH) over the saline control peak concentration of 67 +/- 20 pmol/L. Aldosterone, PRL, T3, and T4 were not significantly affected after L-692,429 administration; however, ACTH treatment significantly increased aldosterone (P < 0.05). These data demonstrate that L-692,429 is a novel nonpeptidyl secretagogue that stimulates a marked, but transient, increase in serum GH levels in the dog.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Higher gonadotrophin surge-attenuating factor bioactivity is found in small follicles from superovulated women.

Ovine and rat pituitary bioassays for gonadotrophin surge-attenuating factor (GnSAF) were utilized to determine whether the level of GnSAF bioactivity in pooled human follicular fluid (hFF) from superovulated women varied according to follicle diameter (< or = 11 mm, 12-15 mm and 16-21 mm follicles examined using the ovine bioassay, or < or = 10 mm, 11-13 mm, 14-17 mm, 18-20 mm, 21-24 mm and > or = 25 mm follicles examined using the rat bioassay). When tested using dispersed ovine pituitary cells, GnSAF bioactivity, expressed in terms of the reduction in gonadotrophin-releasing hormone (GnRH)-induced LH secretion, was inversely related to follicle diameter (P < 0.01). In response to 5 microliters hFF/well from follicles of < or = 11, 12-15 and 16-21 mm diameter, GnRH-induced LH secretion was reduced to 40.5 +/- 6.9%, 65.2 +/- 6.6% and 83.7 +/- 7.9% of control respectively. A similar inverse relationship was observed when a second batch of hFF samples from different sized follicles was tested using rat pituitary cell monolayers. Expressing GnSAF bioactivity in terms of the dose required to suppress GnRH-induced LH secretion by rat pituitary cells to 50% of the maximal suppression observed (ED50), the three smallest follicle size pools contained the most GnSAF (ED50 values of 0.13, 2.79 and 5.36 microliters hFF/well from follicles of < or = 10, 11-13 and 14-17 mm respectively). The ED50 values for follicles of 18-20, 21-24 and > or = 25 mm were 8.81, 27.1 and 60.0 microliters hFF/well respectively. Thus hFF from follicles < or = 11 mm was over 450 times more potent than hFF from follicles > or = 25 mm in suppressing GnRH-induced LH release. The ED50 values for inhibin bioactivity (measured as the suppression of basal FSH secretion from rat pituitary monolayers) were much less variable than those for GnSAF bioactivity (between 0.85 and 0.13 microliters hFF/well). Inhibin immunoreactivity, measured by a two-site immunoradiometric assay, followed the same pattern as inhibin bioactivity with lowest concentrations in the smallest follicles (41.96 ng/ml) and highest concentrations in the three largest follicle size groups (56.48-64.48 ng/ml). The specific effects of inhibin on GnRH-induced LH and basal FSH release in these pituitary bioassays were determined by incubating culture dishes with pure recombinant human inhibin at doses of 0.025-25 ng/well. In both the sheep and rat pituitary monolayers, basal FSH was suppressed (ED50 = 0.02 and 0.16 ng/well respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Circulating gonadotrophin surge-attenuating factor from superovulated women suppresses in vitro gonadotrophin-releasing hormone self-priming.

A perifusion system based on ovine pituitary tissue explants was used to investigate the effects of follicular fluid (hFF) and serum from superovulated women on pituitary responsiveness to gonadotrophin-releasing hormone (GnRH). The specific aims of the study were to determine both if gonadotrophin surge-attenuating factor (GnSAF) bioactivity is present in the peripheral circulation as well as in the follicles of superovulated women and if GnSAF suppresses GnRH self-priming in vitro. Two pulses of GnRH, 1 h apart, produced marked peaks in LH secreted from control chambers, with GnRH self-priming evident in the significant difference between the first (134.4 +/- 1.7 - 232.1 +/- 24.0% of basal secretion) and second (183.9 +/- 15.8 - 313.9 +/- 14.0% of basal secretion) LH peaks. Both follicular fluid and serum pooled from two different groups of women produced marked suppression of the first (unprimed) and second (primed) LH peaks. The hFF reduced the first LH peak to 69.6 +/- 7.8 and 60.2 +/- 9.7% and the second LH peak to 57.4 +/- 6.7 and 42.6 +/- 6.5% of control LH secretion. Overall, the serum reduced the first and second LH peaks to 76.8 +/- 4.2 and 62.9 +/- 3.6% of control respectively. These results demonstrated that GnSAF bioactivity suppresses GnRH self-priming, and is present in both the peripheral circulation and hFF. The same material administered to dispersed ovine pituitary monolayers produced similar marked suppression of GnRH-induced LH secretion, with approximately 50-fold less GnSAF bioactivity in serum compared with hFF. Combined doses of oestradiol and progesterone, or hFF from large follicles containing little GnSAF, produced stimulation of GnRH-induced LH secretion and GnRH self-priming (second peaks 78.1 +/- 38.9 and 27.4 +/- 15.7% respectively higher than first peaks). Thus, in conclusion, GnSAF in hFF and serum markedly attenuated both unprimed and primed pituitary response to GnRH, virtually abolishing the GnRH self-priming effect.

Animals↗
PubMed1994

Induction of delayed afterdepolarizations and triggered arrhythmias in isolated Purkinje fibers: comparison of resibufogenin and acetylstrophanthidin.

The purpose of this study was to compare the electrotoxicological effects of resibufogenin (RBG) (n = 14) with acetylstrophanthidin (AS) (n = 14) to induce delayed afterdepolarization (DAD) and triggered activity (TA), and their alteration of the electrophysiological properties in sheep cardiac Purkinje fibers using the extracellular electrograms, signal averaging, and standard microelectrode techniques simultaneously. The results indicated: 1) Lower toxic dose of RBG (0.52 mumol.L-1) and AS (0.25 mumol.L-1) induced intracellular and extracellular DAD (DAD-I and DAD-E) at pacing cycle length of 990 and 690 ms. 2) Higher toxic dose of RBG (2.6 mumol.L-1) and AS (5.0 mumol.L-1) induced DAD and TA, nonsustained or sustained premature action potential and oscillatory potentials; 3) At the beginning period of superfusing the drugs, both RBG and AS caused changes of the electrophysiological characteristics. This study demonstrates that the electro-toxicological characteristics and electrophysiological properties of RBG are similar to that of AS and suggests that RBG belongs to the family of digitalis-like drugs.

Action Potentials↗
PubMed1993

Formation of eosinophilic and monocytic intradermal inflammatory sites in the dog by injection of human RANTES but not human monocyte chemoattractant protein 1, human macrophage inflammatory protein 1 alpha, or human interleukin 8.

Equilibrium binding studies on canine mononuclear and granulocytic cells allow the identification of a single high affinity receptor for the human C-C chemokine RANTES (dissociation constant, 14 +/- 8 pM), that, in contrast to the human RANTES receptor, has no affinity for human macrophage inflammatory protein 1 alpha (hMIP-1 alpha). A single intradermal injection of hRANTES in dog resulted in eosinophil- and macrophage-rich inflammatory sites within 4 h. Cell infiltration peaked at 16-24 h after hRANTES injection. There was histological evidence of intravascular activation of eosinophils at 4 h, although eosinophils in the vasculature and interstitium contained apparently intact granules. Monocytes were the predominant cells adherent to venular endothelium at 16-24 h. Human MIP-1 alpha elicited no response in canine dermis, whereas monocyte chemoattractant protein 1 caused mild perivascular cuffing with monocytes. In contrast, human interleukin 8 induced a neutrophilic dermal infiltrate that was maximal by 4 h after challenge. This provides the first direct evidence in vivo that RANTES has significant proinflammatory activity and, in addition, could be a mediator in atopic pathologies characterized by eosinophilic and monocytic inflammatory responses.

Animals↗
PubMed1993

Translation initiation complex formation with 30 S ribosomal particles mutated at conserved positions in the 3'-minor domain of 16 S RNA.

Escherichia coli 30 S ribosomal subunits containing in vitro (phage T7 RNA polymerase-generated) 16 S rRNA, both wild-type and mutant, were examined by toeprinting. These synthetic particles were used to compare the effects of the absence of base modification and of specific nucleotide substitutions in conserved sequence regions of the RNA on the assembly of mRNA, tRNAs and 30 S particles into a translational initiation complex. Initiation factor-3-dependent selection of tRNA(fMet) from a mixture of tRNA(fMet) and tRNA(Phe) occurred with all particles, although 20 times less initiation factor-3 was needed for the synthetic particles, including the mutants. Whereas isolated 30 S particles or those reconstituted with isolated RNA did not distinguish between tRNA(fMet) and tRNA(Phe) for ternary complex formation in the absence of initiation factor-3 (intrinsic selection ability), the synthetic particles preferred tRNA(fMet). The difference between the natural and synthetic particles appears to be due to the absence of certain base modifications, but not m2(6)A, in the synthetic RNA. Synthetic particles containing the mutation U1512C, which converts the universal U.G pair to C.G enhanced both tRNA(fMet) binding and selectivity, although other mutations at that site, namely U1512G, G1523A and U1512C/C1524U, had no such effect. Mutants U1498G and G1401C/C1501G, both located in a highly conserved single-stranded region of the 3'-minor domain, also enhanced tRNA(fMet) selectivity, in this case by reducing complex formation with elongator tRNA. Complex formation between elongator tRNA and the G1401C/C1501G mutant was reduced to almost undetectable levels. The results also indicated that the association rate for initiation complex formation for G1401C/C1501G was considerably lower than for the wild-type sequence. This result had not been detected by standard tRNA-30 S binding assays. Overall, the data suggest that (some of) the 16 S rRNA base modifications as well as the tertiary structure around the decoding site act to desensitize the intrinsic selection ability of the ribosome for tRNA(fMet).

Base Sequence↗
PubMed1993

Functional effects of a G to U base change at position 530 in a highly conserved loop of Escherichia coli 16S RNA.

Any base change at position 530 introduced into Escherichia coli on a multicopy plasmid leads to cell death [Powers & Noller (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 1042-1046]. It was suggested that these mutants cannot carry out chain elongation. To define more precisely the function of base 530, we have studied ribosomes in which G530 was mutated to U530. In vivo, U530 16S rRNA was incorporated into 30S subunits and could combine with 50S to make 70S ribosomes. 16S rRNA in vitro transcripts containing U530 were assembled into 30S ribosomes, and their activity was tested in defined steps of protein synthesis. Mutant 30S ribosomes were as active as wild-type in poly(U)-dependent poly(Phe) synthesis, P- and A-site tRNA binding, and 30S initiation complex formation. 30S initiation complexes, in the presence of 50S, could react with puromycin like the wild-type. The rate, extent, and position of cross-linking of AcVal-tRNA in the P site to 16S RNA were identical in mutant and wild-type ribosomes. Although there appeared to be no defect in 70S initiation complex formation or in direct A-site binding of Phe-tRNA dependent on poly(U), U530 30S ribosomes were nevertheless defective in carrying out synthesis of fMet-Val dipeptide using natural mRNA. Mutant 30S ribosomes were also refractory to streptomycin-induced misreading although no misreading was observed in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1993

Effects of gonadotrophin surge-attenuating factor on the two pools of gonadotrophin-releasing hormone-induced luteinizing hormone secretion in vitro.

In order to study the in-vitro mechanism of action of gonadotrophin surge-attenuating factor (GnSAF), ovine pituitary monolayers were incubated for 48 h either with steroid-free follicular fluid from women in whom ovulation had been induced or oestradiol or progesterone. Monolayers were also incubated with 10-30 and > 30 kDa follicular fluid fractions. The effect of these preparations on gonadotrophin-releasing hormone (GnRH)-induced luteinizing hormone (LH) secretion was then determined by incubation with GnRH for between 15 and 240 min. Incubation with steroid-free follicular fluid resulted in the significant attenuation of both the acutely releasable LH pool (LH 54.3 +/- 3.0% of control secretion at 15 min of GnRH incubation) and the reserve LH pool (LH 36.8 +/- 1.6% of control secretion at 240 min GnRH incubation). The 10-30 kDa follicular fluid fraction had similar effects while the > 30 kDa follicular fluid fraction significantly stimulated GnRH-induced LH secretion, with concentrations up to 134.0 +/- 8.6% of controls. Oestradiol or progesterone at doses of 1000 nmol/l/well did not significantly reduce any aspect of GnRH-induced LH secretion (never < 95.1 +/- 15.1% of controls). These results demonstrate that GnSAF markedly attenuates both the acutely releasable and reserve pools of GnRH-induced LH secretion. Inhibin, oestradiol and progesterone are not responsible for the marked attenuation of either the initial or reserve pools of GnRH-induced LH secretion.

Animals↗
PubMed1993

Head CT scanning versus urgent exploration in the hypotensive blunt trauma patient.

In hypotensive blunt trauma patients with a diminished level of consciousness, it may be difficult to decide whether to proceed with immediate head CT scanning or urgent laparotomy or thoracotomy. The purpose of this study was to determine the frequency of emergency craniotomy and urgent laparotomy or thoracotomy in a group of 734 blunt trauma patients with initial hypotension (BP < 90 mm Hg systolic) admitted to the eight level I and II trauma centers in North Carolina. The mean initial systolic blood pressure was 64 +/- 26 mm Hg, and the mean Trauma Score was 8 +/- 5.8. Serious head injury (AIS head > or = 3) was present in 40% (293 of 734). Of 734 patients studied, 9.4% (69 of 734) died in the emergency department. Head CT scanning was performed on 47% (344 of 734) and produced positive results for 26% (202 of 734). Emergency craniotomy for intracranial hemorrhage was performed on 2.5% (18 of 734) (ten subdurals, three epidurals, and five other intracranial hemorrhages). Twenty-one percent (154 of 734) underwent urgent laparotomy, thoracotomy, or both. Overall hospital mortality for hypotensive blunt trauma patients was 36% (263 of 734). Although serious head injury occurs commonly (40%) in hypotensive blunt trauma patients, frequency of urgent laparotomy (21%) is 8.5 times greater than emergency craniotomy for intracranial hemorrhage (2.5%). This information may be used by trauma teams in prioritizing care for hypotensive blunt trauma patients.

Abdominal Injuries↗
PubMed1993

Impact of pedestrian injury on inner city trauma services.

This report describes the epidemiology of pedestrian injury in four inner metropolitan local government areas of Sydney. These data were obtained from the Roads and Traffic Authority of New South Wales. The spectrum of injury and clinical outcome was defined in patients with an Injury Severity Score (ISS) > 15 admitted from the study area, during a 1 year period, to the four inner metropolitan teaching hospitals. The incidence of pedestrian death was 3.3 times the state average of 32/10(6)/year. An average of 235 pedestrians, injured in the study area, were hospitalized each year during the period 1987-89. On average 24 pedestrians died each year, seven at the scene and 17 in hospital. Fifty patients (ISS > 15) were admitted to the four teaching hospitals during a 1 year period 1990-91. Forty-five were adults and five children. Multiplicity of injury was seen in 68% of patients. The pelvis and lower extremities were involved in 70%, the head in 66% and chest in 42%. The hospital mortality rate was 30% with five patients dying on the first day from blood loss and nine dying during subsequent days from head injury. This study has important implications for trauma service development. Successful clinical management of the severely injured pedestrian requires close co-operation between pre-hospital and hospital care providers. An integrated hospital trauma team response is mandatory to ensure appropriate management of what is often a shocked, hypoxic, head-injured patient.

Abbreviated Injury Scale↗