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Biomedical subjects

W A Murphy

Publications and source records attributed to W A Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1991

Human growth hormone-releasing hormone analogues with much improved in vitro growth hormone-releasing potencies in rat pituitary cells.

Enhancement of the amphiphilic alpha-helical properties of the central and C-terminal regions of growth hormone-releasing hormone (GRH) by substitution with helix-favouring amino acids, particularly Ala, can result in significant improvements in GH-releasing potencies using monolayer cultures of rat pituitary cells, a system which reflects analogue receptor affinity rather than effects of structural modifications on pharmacokinetic properties. For instance, previously reported, helix-enhanced [Ala15]GRH-(1-29)NH2 was presently 5 times more potent than [Gly15]GRH-(1-29)NH2 in this assay. The extent and importance of alpha-helical character further towards the N-terminus is less clear since Chou-Fasman probability calculations indicate also the possibility of beta-bend formation in the 6-10 region. However, replacement of Asn8 with Ala resulted in a 4-fold improvement in potency and when this was combined with Ala15 to give [Ala8,15]GRH-(1-29)NH2 a 15-fold increase in potency was achieved and combination of D-Ala2, Ala8 and Ala15 gave a 27-fold increase indicating that the effects of all of these modifications were additive. Computer analysis furthermore revealed that substitution of Ala for Ser in position 9 should also increase alpha-helix probability from 0.93 to 1.05. [D-Ala2,Ala8,9,15]GRH- (1-29)NH2 was 49 times more potent than GRH itself making it by far the most potent analogue thus far reported in an in vitro assay system. The Ala8 and Ala9 substitutions were also effective in improving the inhibitory potency of a GRH receptor antagonist, [D-Arg2,Leu27]GRH-(1-29)NH2.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Imaging bone tumors in the 1990s.

Progress in bone tumor management has occurred as a result of cooperation among surgeons, oncologists, pathologists, and radiologists. During the 1990s radiologists will contribute to care of patients with bone tumors in major ways. Tumor detection and preliminary diagnosis will be accomplished by radiography. Tumor local extent will be assessed by magnetic resonance imaging (MRI) and to a lesser degree by computed tomography (CT). Distant spread of malignancy will be documented by radionuclide scintigraphy (skeleton) and by CT (lungs). The combined estimate of local extent and distant spread will assure adequate staging before definitive management decisions. Preoperative closed percutaneous biopsy for histologic diagnosis will be accomplished on an outpatient basis under fluoroscopic or CT guidance. Arteriography will be employed for delivery of local chemotherapy. Some combination of arteriography, MRI, and MR spectroscopy will be used to evaluate tumor response. After limb-salvage surgery, MRI will sequentially assess the tumor bed; bone scintigraphy and CT will detect skeletal and pulmonary metastases. The radiologist's role will undergo continuous redefinition.

Bone Neoplasms↗
PubMed1991

Calcaneal and pelvic fractures: diagnostic evaluation by three-dimensional computed tomography scans.

A major application of three-dimensional (3D) computed tomography (CT) is in the imaging of the skeleton. 3D CT has a potentially important role in determining the presence, type, and extent of fractures, especially of the calcaneus and pelvis. The objective of this study was to compare the diagnostic sensitivity and specificity of 3D CT, CT slices, and plain radiography in the detection and characterization of calcaneal and pelvic fractures. 3D CT reconstructions were obtained by two methods, surface reconstruction and volumetric techniques. Twenty-eight patients were imaged with CT, 3D CT, and plain radiography. The opinion of a musculoskeletal radiologist with access to all images plus clinical history, surgical findings, and follow-up findings was taken as truth. Four additional musculoskeletal radiologists read these cases in a blinded fashion and ranked the modalities with regard to perceived utility. Receiver operating characteristic analysis was used to determine the relative value of each modality in terms of diagnostic quality. All imaging modalities performed comparably in the diagnosis of fractures. CT slices and plain-films were the most useful for more difficult diagnostic tasks such as fracture stability, and the presence of comminution and estimation of the number of fragments. The results suggest that for skeletal areas with complicated anatomy (such as the pelvis and calcaneus), the diagnostic value of 3D CT is often equivalent to that of conventional methods.

Acetabulum↗
PubMed1991

X-linked hypophosphatemia: skeletal mass in adults assessed by histomorphometry, computed tomography, and absorptiometry.

PURPOSE AND PATIENTS AND METHODS: X-linked hypophosphatemia (XLH) is the most common inherited form of rickets, yet its influence on skeletal mass in adulthood is controversial and incompletely characterized. Accordingly, we measured bone mass at several skeletal sites using histomorphometric and radiographic techniques in 19 adults (four men) with XLH (age range 20 to 66 years). Most subjects had not received medical therapy for XLH since puberty. RESULTS: Eight of 14 subjects who underwent transiliac bone biopsy had an elevated cancellous bone volume (osteoid and calcified bone), and the group's mean value was supranormal (p less than 0.01). Mineralized bone volume, however, was above normal in only three subjects (NS). Another measure of trabecular bone density, vertebral mineral density by computed tomography, was elevated in three of 13 subjects, and the mean value of the group was increased (p = 0.05). Integral spine bone mineral density (BMD) assessed by dual photon absorptiometry (DPA) was elevated in six of 16 subjects, and the mean was also above normal (p less than 0.01). However, total body calcium, total body BMD (both by DPA), and forearm bone mineral content assessed by single photon absorptiometry (predominantly cortical bone) were normal in almost all subjects, as were the group means for these parameters. Mean regional BMD (by DPA) was below normal in the upper and lower limbs (p less than 0.001) and above normal in the spine (p less than 0.005) and ribs (p less than 0.01). There was no relationship between these indices of bone mass and either biochemical or clinical parameters of disease severity, although men tended to have higher z-scores for axial bone density than premenopausal women whose values, in turn, tended to be higher than those in postmenopausal women (NS). CONCLUSION: We conclude that axial bone mass tends to be increased in adults with XLH, sometimes dramatically so, and this is only partially attributable to hyperosteoidosis. Peripheral bone mass, however, tends to be diminished. Despite these group trends, most adults with untreated XLH have normal indices of bone mass as assessed by a variety of techniques at the commonly used measurement sites. These findings suggest that "osteoporotic" fractures are unlikely to develop as a late complication of XLH in adults.

Absorptiometry, Photon↗
PubMed1991

Quality assessment in an ambulatory care unit: do training and responsibility conflict?

The authors determined the characteristics of musculoskeletal radiographic misinterpretations by 2nd-year internal medicine residents (IMRs) and board-certified emergency department physicians (EDPs) in an ambulatory care unit (ACU) compared with interpretations rendered by staff radiologists. The type (false-positive error [F+] or false-negative error [F-]), site, nature, and clinical significance of errors were assessed. Two hundred thirty-three cases met study requirements; EDPs interpreted 165 cases; IMRs, 68. Discrepancies were found in 55 cases (24%) (44 F- and 11 F+). IMRs committed more F- than did EDPs (25% vs 16%). The most common sites of examination were ankle, finger, and elbow. IMRs missed more periarticular fractures (75%) than did EDPs (33%). The errors were judged "clinically significant" in 7.8% of cases; IMRs made more of these errors than did EDPs (13% vs 4%). Radiologist overview reduced clinically significant errors fivefold. The authors conclude that patient care is well served by clinician-radiologist synergism. The inclusion of selected basic radiologic principles in ACU residency training programs may improve non-radiologists' effective use and interpretation of radiologic examinations.

Adolescent↗
PubMed1991

Photostimulable phosphor digital radiography of the extremities: diagnostic accuracy compared with conventional radiography.

A direct comparison was made between digital and conventional radiographs to assess the relative accuracy of a photostimulable phosphor digital imaging system in detecting and localizing minor trauma in the extremities. Matched sets of images were obtained on 103 patients who came to the emergency department for radiographs of the hand, wrist, foot, or ankle. One set was obtained with a conventional screen/film system. The other set was obtained with photostimulable phosphor digital cassettes. The two sets of images of each patient were independently interpreted by three radiologists in a blinded fashion. The findings of each of these three readers were compared with the consensus opinion of two different radiologists. Receiver-operating-characteristic (ROC) curves were plotted for each of the three readers, areas under the curves were calculated, and true-positive fractions were determined at false-positive fractions of 0.1. Although no significant differences in the areas under the ROC curves for the two imaging systems were detected, conventional radiography showed a slight advantage. However, when true-positive fractions for fracture detection were compared at false-positive fractions of 0.1 a statistically significant difference was shown, with conventional screen/film radiography being more sensitive. This study raises questions about the use of currently available photostimulable phosphor systems for imaging trauma of the extremities and suggests that those systems should not be used exclusively.

Adult↗
PubMed1990

Analogues of growth hormone-releasing factor (1-29) amide containing the reduced peptide bond isostere in the N-terminal region.

Previous peptide structure-activity investigations employing the psi[CH2NH] peptide bond isostere have produced antagonists when inserted into various sequences. These include bombesin, in which the incorporation of Leu13 psi[CH2NH]Leu14 produced a potent antagonist, and tetragastrin, with which Boc-Trp-Leu psi[CH2NH]Asp-Phe-NH2 is an antagonist. In this study, we chose to investigate the effect of this isostere on growth hormone-releasing factor (1-29) amide. Analogues were prepared by solid-phase synthesis and the isosteres incorporated by racemization-free reductive alkylation with a preformed protected amino acid aldehyde in the presence of NaBH3CN. The aldehydes were prepared by the reduction of the protected N,O-dimethyl hydroxamates with LiAlH4 at 0 degrees C. The purified analogues were assayed in a 4-day primary culture of male rat anterior pituitary cells for growth hormone (GH) release. Potential antagonists were retested in the presence of GRF(1-29)NH2. The following results were obtained: At position 5-6, a very weak agonist was produced with much less than 0.01% activity. Incorporation of the isostere in positions 1-2, 2-3, and 6-7 gave weak agonists with approximately 0.1% activity. Agonists with 0.39% and 1.6% activity were produced by incorporation at 10-11 and 3-4, respectively. The analogue [Ser9 psi[CH2NH]Tyr10]GRF(1-29)NH2 was found to be an antagonist in the 10 microM range vs 1 nM GRF and had no agonist activity at doses as high as 0.1 mM.

Amino Acid Sequence↗
PubMed1990

Magnetic resonance imaging of peripheral nerve sheath tumors. Assessment by numerical visual fuzzy cluster analysis.

A retrospective, nonblinded review of ten nerve sheath tumors (four malignant) selected for pathologic proof and complete magnetic resonance (MR) evaluation was performed to assess the primary tumor location, signal pattern, and extent of reactive zone. A modification of visual fuzzy cluster analysis (VFCA) that emphasized the number of visual fuzzy clusters in each mass was developed to assess the neural tumors. The MR findings were correlated with the findings at surgery and histopathology. There were six men and four women, aged 19 to 62 years (mean, 43). Nine tumors involved the lower extremity. In all tumors, MRI correctly identified the nerve trunk of origin. Tumor dimensions were generally overestimated by MRI. Three internal signal patterns were observed: homogeneous (1/1 benign), finitely inhomogeneous (5/5 benign), and hectically inhomogeneous (4/4 malignant). The number of visual fuzzy clusters (VFCRs) for each sequence did not allow reliable separation of benign and malignant entities, but when considered in aggregate, benign and malignant lesions segregated in different clusters. This implies that the likelihood of malignancy increases as the number of MR-identifiable tissue types per lesion increase. Three types of reaction (edema) were observed best on long repetition time/echo time (TR/TE) sequences, confined to immediate peritumoral region, intracompartmental, and extracompartmental. The first two patterns correlated well with clinicopathologic findings; however, the third pattern did not. Separation of indolent (benign) cellular masses from aggressive (malignant) ones by MR characteristics is difficult but VFCA shows promise for aiding this differentiation and deserves further investigation in larger study populations.

Adult↗
PubMed1990

Analysis of cardiovascular and pulmonary responses to endothelin-1 and endothelin-3 in the anesthetized cat.

Cardiovascular and pulmonary responses to endothelin (ET)-1, ET-3 and neuropeptide Y (NPY) were investigated in the anesthetized cat. ET-1, 0.1 to 1 nmol/kg i.v., decreased or elicited biphasic changes in arterial pressure (AP), whereas ET-3, in the same doses, decreased AP. Both ETs increased cardiac output (CO) and, at the highest doses, a secondary decrease in CO was observed. NPY, 0.3 to 3 nmol/kg i.v., increased AP and at the highest dose decreased CO. All three peptides had inconsistent effects on right ventricular contractile force and increased central venous pressure. ET-1 at lower doses increased heart rate (HR) and, at 1 nmol/kg, caused a biphasic change. ET-3 increased HR, whereas NPY decreased HR. Systemic vascular resistance (SVR) was increased by NPY and decreased by ET-3, whereas ET-1 elicited biphasic changes. ET-1 and ET-3 increased pulmonary arterial pressure, left atrial pressure and caused biphasic changes in pulmonary vascular resistance (PVR). NPY had no significant effect on PAP or PVR. When pulmonary blood flow was maintained constant, ET-1 and ET-3 had only pulmonary vasoconstrictor activity, whereas NPY and the ET analog had no significant effect. The increase in SVR in response to NPY, the decrease in response to ET-3 or the biphasic change in response to ET-1 were not modified by meclofenamate, hexamethonium or propranolol. Increases in HR in response to ET-1 and ET-3 were reduced by the beta receptor and ganglionic blocking agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of porcine and rat endothelin and an analog on blood pressure in the anesthetized cat.

Arterial responses to a wide range of doses of porcine and rat endothelin and a monocyclic analog were compared in the anesthetized cat. Injections of the porcine peptide in doses of 0.01-0.1 nmol/kg i.v. decreased systemic arterial pressure in a dose-related manner, whereas doses of 0.3 and 1 nmol/kg i.v. elicited biphasic responses. The rat peptide, in doses of 0.03-1 nmol/kg i.v., also decreased arterial pressure in a dose-related fashion, whereas injection at 3 nmol/kg i.v. caused a biphasic response. With both peptides the biphasic response was characterized by an initial short-lived decrease followed by a secondary sustained increase in pressure. The monocyclic porcine analog in doses of 3-30 nmol/kg i.v. had no significant effect on arterial pressure. Both peptides increased cardiac output, and changes in peripheral vascular resistance in response to both peptides were not altered by sodium meclofenamate. These data suggest that arterial depressor responses to porcine and rat endothelin are similar and dose-dependent. However, the porcine peptide has 3-fold greater pressor activity in the cat. The lack of effect with the monocyclic porcine analog suggests that the two disulfide linkages are necessary for activity.

Anesthesia↗
PubMed1989

Correlation of MRI images with histology in avascular necrosis in the hip. A preliminary study.

The role of MRI in identifying the tissue level changes in the femoral head was investigated in five patients diagnosed as having avascular necrosis by radiology, scintigraphy, and MRI (0.35 Telsa). Radiographic scoring by the Ficat and Arlet system showed one hip with stage I, one stage II, two stage III, and one stage IV changes. The histologic features of core biopsy specimens obtained during decompression of the femoral heads were compared to the preoperative T1 and mixed T1/T2-weighted MR images. The cores varied with respect to their distance from the subchondral bone (7-23 mm) and length (19-45 mm). At the subchondral end of the core tract, low T1-weighted images corresponded to marrow fibrosis (5 cases) and in three of five cases to increased trabecular bone volume (TBV = 44-50%). Subjacent areas of diffusely decreased MR signal corresponded to marrow fibrosis and necrosis, with a relatively normal TBV (17-28%). The distal ends of the core tracts showed normal fatty marrow and a normal MR signal. The observations affirm that the MR signal intensity is largely reduced as a function of marrow degeneration and loss of fat content, but the signal is not predictive of particular histotypic morphologic patterns.

Adult↗
PubMed1989

Clinical evaluation of serum fructosamine in monitoring elderly outpatient diabetics.

Recently, new serum glycated protein assays (ie, serum fructosamine) have been developed. Fructosamine assays objectively monitor short-term glycemic control and, when used in conjunction with HgA1C, enhance the clinical information obtained and greatly aid in the clinical management of diabetes. Because they rely on glycation of serum proteins, the clinical utility of these assays in the elderly may be altered secondary to the hypoproteinemia that often is seen in these states. Therefore, we investigated the role of glycated serum proteins (ie, fructosamine level) in monitoring elderly diabetics over a 4-month period of observation. We found that the fasting blood glucose over the 4-month period correlated well with the serum fructosamine activity (r = 0.79, P less than .001) and HgA1C (r = 0.78, P less than .001). In addition, we found that the mean daily glucose, as determined by outpatient monitoring, correlated well to both the fructosamine activity (r = 0.66, P less than .001) and HgA1C (r = 0.74, P less than .001). We found no effect on the measurement of the fructosamine assay by the level of albumin seen in these patients. Our study suggests that serum fructosamine and HgA1C are equally effective in monitoring the elderly patient, as has been established in the younger diabetic, and no correction need be made in the fructosamine assay to compensate for variable serum protein levels seen clinically in the elderly.

Aged↗
PubMed1989

X-linked hypophosphatemia in adults: prevalence of skeletal radiographic and scintigraphic features.

The radiologic studies of 38 essentially untreated adults with X-linked hypophosphatemia (XLH) were reviewed to determine the prevalence of radiologic features, to compare the findings in men and in women, and to elucidate the natural history of the disease by comparing the findings in young, intermediate-age, and older patients. Bone-reinforcement lines were common, but no characteristic mineral mass alteration was established. Looser zones were more prevalent in older subjects. Osteoarthritis was common, occurring in the ankles, knees, feet, sacroiliac joints, and wrists. Enthesopathy was infrequent in the younger group but was present in every member of the intermediate and older groups and was often accompanied by extra ossicles. Curvatures of the lower-extremity long bones were common in all age groups. Three new skeletal alterations in XLH were found to be common: flaring of the iliac wings, trapezoidal distal femoral condyles, and alterations in talar morphology, including shortening of the talar neck and flattening of the talar dome. Technetium-99m methylene diphosphonate scintigrams of 17 subjects were often abnormal, depicting bowing deformity and focal tracer accumulation in diaphyseal cortices and in periarticular and extraarticular regions. The mean metabolic index was moderately elevated (4.0). Both radiographic and scintigraphic findings were more severe in men, consistent with hemizygosity. The natural history of untreated XLH in both sexes is characterized by the development of a variety of age-related skeletal abnormalities during adulthood.

Adult↗