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Biomedical subjects

W A Murphy

Publications and source records attributed to W A Murphy.

At least 91 records · Page 5Linked to original sources
PubMed1989

Shoulder joint: arthrographic CT and long-term follow-up, with surgical correlation.

One hundred two computed tomographic (CT) arthrograms of the shoulder were retrospectively reviewed and compared with conventional double-contrast arthrograms from 101 patients (24 females and 77 males aged 9-70 years). One- to 4-year follow-up was obtained in 84 patients, 40 of whom underwent open-shoulder surgery or arthroscopy. Morphology of the normal portions of each labrum was categorized according to length, width, and tip shape. Correlation between morphology and age was weak, but abnormal labra were more common in younger patients. Conventional radiography was more accurate for detecting bony glenoid margin fractures, but CT was more accurate for detecting Hill-Sach fractures. CT was also more reliable than conventional arthrography in the detection of rotator cuff tears. Hence, few if any conventional radiographs are necessary between contrast material injection and CT imaging. A reduction in the number of images obtained will result in decreased radiation dose, less cost, and shorter examination time without loss of diagnostic accuracy.

Adolescent↗
PubMed1989

Effects of a novel bombesin antagonist analogue on bombesin-stimulated gastric acid secretion and growth hormone release in the pentobarbital-anesthetized rat.

A new and specific bombesin receptor antagonist analogue, Leu13 psi [CH2NH]Leu14-bombesin, was studied for inhibition of bombesin-stimulated gastric acid secretion in pentobarbital-anesthetized rats. The analogue potently inhibited bombesin-stimulated gastric acid secretion in a dose-dependent fashion, exhibiting an ID50 of 0.66 mumol/250 g, which corresponds to a molar ratio of bombesin to antagonist of approximately 1:12. This agrees well with antagonist to agonist potency ratios previously reported for inhibition of bombesin-stimulated amylase release from guinea pig pancreatic acinar cells and the growth of murine Swiss 3T3 cells, suggesting functional similarities between the receptor sites involved. Conversely, the analogue failed to inhibit bombesin inhibition of growth hormone release in the sodium pentobarbital-anesthetized rat model and was, in fact, a weak agonist at higher dose levels. This indicates either that this system is not particularly bombesin-specific or that bombesin receptor recognition and signaling requirements are substantially different in the gut and hypothalamus.

Animals↗
PubMed1989

Ascending lower limb phlebography: comparison of ioversol and iothalamate meglumine.

Fifty patients undergoing ascending phlebography of a lower limb were evaluated, in a randomized double-blind fashion, to compare the efficacy, patient tolerance, and safety of two different contrast agents. Ioversol-240 (MP-238), a new nonionic agent, and iothalamate-202 (Conray 43), an established ionic agent, were the contrast agents used. Twenty-five patients were injected with iothalamate and 25 with ioversol. The phlebograms were evaluated for diagnostic quality and the patients for symptoms, with special reference to complaints of heat and pain. No significant difference was demonstrated between the two agents in either examination quality or patient tolerance. No major contrast-related reactions were recorded. We conclude that ioversol-240 appears to be a safe and acceptable alternative to iothalamate-202.

Adult↗
PubMed1989

Preliminary trial of minidose heparin prophylaxis for painful sickle cell crises.

Four patients with well-documented severe recurrent painful sickle cell crises received 12-month courses of self-administered minidose heparin (5000-7500 units every 12 hours). Patients were evaluated weekly or bi-weekly for symptoms and signs of sickle crises. The observations were compared with identical observations during 12 months off heparin (control). Prior to starting heparin, baseline laboratory values were established, including hematocrits, platelet counts, and plasma coagulation factors. Bone density was evaluated by radiologic measurement of metacarpal cortical width and by forearm transmission osteodensitometry. Laboratory values were repeated at each visit; bone density was reevaluated every 6 months. At each visit clinical status for the preceding 1-2 weeks was classified as: no pain (I), minor pain controllable by non-prescription medications (II), pain requiring office or emergency room admissions for parenteral narcotics (III), hospitalized for about 3 days for pain crisis (IV). One patient completed a single 2-year cycle; one patient completed 2 cycles (followed 4 years), and 2 patients have undertaken 3 cycles (followed greater than or equal to 6 years). No treatment-related complications occurred requiring discontinuation of heparin. Thrombocytopenia was not observed. There was no evidence of progressive osteopenia. All patients improved while receiving heparin; 1 moderately, 3 markedly. Cumulative data (8.7 patient years on heparin, 12 control years) revealed a 73% reduction in days of hospitalization per year and 74% reduction in hours spent in emergency rooms per year during heparin administration. Pretreatment pain patterns recurred when heparin was discontinued.

Adult↗
PubMed1989

X-linked hypophosphatemia: a clinical, biochemical, and histopathologic assessment of morbidity in adults.

Research and management of XLH have concentrated on the disease in childhood, and the natural history and morbidity of XLH in adult life are thus poorly understood. We have studied 22 adults (6 men) with XLH to clarify these aspects of this most common inherited form of rickets and osteomalacia. Most study participants had presented with rickets in early childhood and had undergone tibial osteotomies on at least 1 occasion. Seventeen individuals had genu varum, 1 had genu valgum, and 4 had straight legs, attributable to successful osteotomies in 2. Five subjects reported increasing lower limb deformity in the late teens or subsequently. Eight subjects complained of bone pain, 6 of whom had radiologic evidence of pseudofractures; pseudofractures were found in 4 additional asymptomatic individuals. None of 16 subjects who underwent transiliac bone biopsy had normal double tetracycline labeling; accordingly, all were considered to have osteomalacia. Bone pain was associated with a relative osteoid volume in excess of 25%. Relative osteoid volume was inversely related to serum 1,25(OH)2D concentration (r = -0.74, p less than 0.02), but unrelated to serum concentrations of calcium and phosphate or their product. Eighteen participants complained of joint pain, predominantly in the knees and ankles. The severity of joint pain correlated with the degree of lower limb deformity (p = 0.011) which, in turn, was related to fasting serum phosphate concentration (r = -0.56, p less than 0.025) and TmP/GFR (r = -0.70, p less than 0.005). Enthesopathy affected 33% of those younger than 30 years, and all those above this age. Nineteen individuals had experienced significant dental problems, most commonly abscess formation. Eight had required complete dental clearance. Twelve women from the group had a total of 22 live births. Fifteen of these were by cesarean section, although radiologic evidence of pelvic narrowing was not found in any subject. Serum ALP was elevated in all but 3 of the 18 untreated subjects. Levels correlated with those of other indices of bone turnover (BGP r = 0.82, p less than 0.005; urine total HP r = 0.60, p less than 0.025; urine free HPr = 0.78, p less than 0.005), but were not related to the degree of osteomalacia found on bone biopsy. Serum levels of iPTH, 25(OH)D, 1,25(OH)2D, and thyroid hormones were generally normal in the untreated patients. We conclude that adults with untreated XLH have osteomalacia that is frequently symptomatic. Even greater morbidity is caused by degenerative joint disease arising from lower limb deformities.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1988

Transient osteoporosis: transient bone marrow edema?

Ten patients with debilitating hip or knee pain were examined with magnetic resonance (MR) imaging. All had conventional radiographs that were either normal or showed nonspecific osteopenia. Nine patients had bone scintigrams that showed focal increased radionuclide uptake in the region of the painful joint. In each case, MR images of the affected joint showed regional decreased signal intensity of the bone marrow on T1-weighted images and increased signal intensity on T2-weighted images. Biopsy results of four patients excluded ischemic necrosis and metastases. The symptoms resolved spontaneously in all cases. The ten patients were followed up for 12-36 months, and there were no recurrences. The authors believe that the findings on MR images represent a transient increase in bone marrow water content. The focal findings on scintigrams confirmed the periarticular distribution of the process and provided evidence of accompanying hyperemia and increased bone mineral metabolism. For lack of a better term and to emphasize the generic character of the condition, the authors termed this condition "the transient marrow edema syndrome."

Bone Marrow↗
PubMed1987

Inhibition of rat prostate tumor growth by an octapeptide analog of somatostatin.

Analogs of a potent octapeptide analog of somatostatin (SRIF) H-(D)Phe-Cys-Tyr-(D)Trp-Lys-Val-Cys-Thr(NH2) were synthesized. Aromatic substitutions for Tyr resulted in little change in inhibitory potency on growth hormone (GH) secretion in the rat. Substitutions for Val or (D)Trp resulted in analogs with diminished activity. Substitution of (D)Nal for (D)Phe increased duration of GH inhibition. Final weights of subcutaneously implanted prostate tumors (R3327) were 41% lower in rats treated with an N-terminal 4-chloro-(D)phenylalanyl analog as compared to vehicle treated controls. The analog had no effect on testicular weight or final plasma testosterone levels. SRIF analogs may represent an alternative treatment for prostate cancer that would be free of the untoward reproductive effects of other treatments (e.g. LH-RH or castration).

Animals↗
PubMed1987

Radiographic assessment of progression in osteoarthritis.

We evaluated methods of grading radiologic progression of osteoarthritis (OA). Sets of radiographs were assessed separately by 8 readers who were blinded to the time sequence. Included were radiographs of patients with OA of the hands (24 pairs), hips (40 pairs), and knees (32 pairs). Most films were taken 12-60 months apart. The relative contribution of individual joints (such as particular interphalangeal joints), of observations (such as narrowing or spurs), and of a single joint compartment (such as the medial or lateral compartment of the knee) toward evidence of OA progression was evaluated, as well as the reliability and concordance of scoring, and the sensitivity in detecting change. In assessing OA of the hand, the greatest sensitivity was achieved by reading a single posteroanterior bilateral hand radiograph for narrowing, spurs, and erosions, and scoring 10 joints (second and third distal interphalangeal, second and third proximal interphalangeal, and trapeziometacarpal joints, bilaterally), using a scale of 0-3. In OA of the hip, a single anteroposterior radiograph assessed for joint space narrowing and cyst formation yielded the greatest sensitivity. In OA of the knee, an anteroposterior radiograph, with weight-bearing, assessed for narrowing, spurs, and sclerosis in both the medial and lateral compartments yielded the greatest sensitivity. These techniques will be useful to the investigator in designing experimental studies and to the clinician in determining the rate of disease progression in an individual patient.

Aged↗
PubMed1987

Differential effects of N-terminal modifications on the biological potencies of growth hormone releasing factor analogues with varying chain lengths.

The excellent retention of biological potencies observed with human growth hormone releasing factor analogues with chains 29-44 amino acid residues long is suddenly lost when further amino acid residues are removed from the C-terminus. For instance, 1-27 and 1-24 exhibited little biological activity (greater than 1%) in vivo and in vitro in the rat. Studies were made to determine whether this was due to conformational changes rather than simply the loss of amino acids needed for direct receptor interactions. These involved the introduction of mild conformational restraint in the N-terminal region by the introduction of D-amino acid residues previously shown to increase the potency of the 1-29 peptide. D-Ala in position 2, responsible for a 40- to 50-fold increase in activity in the 1-29 species, resulted in little increase in the potency of 1-27 or 1-24 sequences. However, N-terminal acetylation, responsible for a 12-fold increase in 1-29 in vivo potency, caused greater than 50-fold increase in 1-27 potency but had little effect on 1-24 potency. Likewise, D-Asn in position 8 was far more effective in increasing the potency of the 1-27 sequence compared to the 1-29 ([D-Asn8]-GRF(1-29)NH2, 220% vs. [D-Asn8, Leu27]-GRF(1-27)NH2, 53%; in vivo]. This differential effect was even more clear in vitro. The highest in vivo potency in the 1-27 series was achieved with [D-Asp3,D-Asn8,Leu27]-GRF(1-27)NH2 (200%); however, this analogue was still far less potent than its 1-29 counterpart (3800%). None of the D-amino acid substitution strategies were effective in increasing 1-22 peptide potencies to detectable levels. The results indicate that the effect of N-terminal substitutions and resulting potencies of the GRFs is very much dependent on chain length, perhaps suggesting that C-terminal amino acids promote conformational effects at the N-terminus and/or vice versa.

Amino Acid Sequence↗
PubMed1987

Solid-phase synthesis and biological properties of psi [CH2NH] pseudopeptide analogues of a highly potent somatostatin octapeptide.

A series of psi [CH2NH] pseudopeptide analogues of a potent somatostatin octapeptide analogue, H-D-Phe-Cys-Try-D-Trp-Lys-Val-Cys-Thr-NH2, were synthesized by using a newly developed solid-phase method for direct introduction of the CH2NH peptide bond isostere. Analogues were obtained in normal yields via a combination of sodium cyanoborohydride mediated reductive alkylation of resin-bound peptide amine with a tert-butoxycarbonyl amino acid aldehyde for introduction of a CH2NH bond and normal solid-phase peptide chemistry. A racemization test on a model pseudodipeptide indicated that no more than 6% racemization took place during the aldehyde preparation and alkylation steps. Analogues were examined for their ability to inhibit growth hormone release in vivo in sodium pentobarbital anesthetized rats and in vitro from cultured rat anterior pituitary cells. Analogues modified at the amide carbonyl of Cys2 and Lys5 showed the highest in vivo activity (20 and 8 times more potent than SRIF, respectively) and in vitro activity (0.17 and 0.67 times as active as SRIF). This compared to in vivo and in vitro potencies of 8000% and 100%, respectively, for the parent analogue. Modification of the other cyclic ring amide carbonyls of Tyr3, D-Trp4, and Val6 or the N- or C-terminal amide carbonyl of D-Phe1 or Cys7 gave analogues with considerably lower in vitro or in vivo potencies. The results appear to offer support for a proposed type II beta-turn solution conformation centered on the D-Trp-Lys portion of SRIF octapeptide analogues, resulting in possible hydrogen-bonding interactions between Tyr3 and Val6 and D-Phe1 and Thr8 residues in the parent peptide. These would then be disrupted by methylene replacement of the carbonyl groups with concomitant loss of biological activity as was observed.

Animals↗
PubMed1987

Multispectral analysis of MR images of the breast.

Preliminary investigations were conducted into the potential of magnetic resonance (MR) images for tissue classification of the breast on the basis of relative signal intensity. Multispectral techniques originally developed by the National Aeronautics and Space Administration for satellite image analysis were used in sequence selection, image data correction, image standardization, and image interpretation. Numerous sequence combinations with varying repetition times (TR) and echo times (TE) were considered, and a triplet was selected consisting of long TR/long TE, short TR/short TE, and an opposed phase sequence with intermediate TR and TE. Correction to remove system-imposed intensity inhomogeneities was required for all images. Image standardization based on fat and pectoral muscle signals was necessary for intercase comparisons. Multispectral images obtained based on this analysis suggest the feasibility of intensity-based image classification.

Breast Neoplasms↗
PubMed1987

Differential binding of somatostatin agonists to somatostatin receptors in brain and adenohypophysis.

In order to improve our understanding of the ligand specificity of somatostatin (SRIF) receptors in pituitary and brain, and to identify analogs that bind to one type exclusively, we compared several new SRIF analogs for competitive binding to pituitary and cerebral cortex membranes. Binding of [125I-Tyr11]SRIF to hypophysis and brain was of high affinity [KD = 0.76 nM (0.2-1.3) and 0.37 nM(0.1-0.8), mean (95% confidence limits)] and was characteristic of binding to one class of sites in both tissues. Competition by several SRIF analogs for such radioligand binding demonstrated that ligand specificity of adenohypophysial receptors was distinctly different from that of cerebral cortex. Two cyclic octapeptides (sequence; see text) bound to pituitary SRIF receptors with high affinity [Ki = 0.85 nM (0.5-1.2) and 0.35 nM (-0.3-0.9)] and were potent inhibitors of GH secretion from primary cultured pituitary cells [EC50 = 0.009 nM (0-0.02) and 0.017 nM (0.01-0.02), respectively]. However, these selective peptides did not compete (Ki much greater than 1 microM) for radioligand binding to brain. Amidation of the C-terminal end appeared to strikingly alter brain SRIF receptor recognition of the substituted ligand. Indeed, such amidation of the parent peptide, (sequence; see text) resulted in a reduced ability to displace labeled ligand from brain sites [Ki = 165.3 nM (47.6-282.9) to 842.2 nM (603.9-1,081)] but did not affect competition for pituitary receptors. Our results indicate that anterior pituitary SRIF receptors (SRIFa) have ligand specificities which are clearly different from those of their brain counterparts (SRIFb).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Multispectral magnetic resonance image analysis.

Multiecho magnetic resonance (MR) scanning produces tomographic images with approximately equal morphologic information but varying gray scales at the same anatomic level. Multispectral image classification techniques, originally developed for satellite imaging, have recently been applied to MR tissue characterization. Statistical assessment of multispectral tissue classification techniques has been used to select the most promising of several alternative methods. MR examinations of the head and body, obtained with a 0.35, 0.5, or 1.5T imager, comprised data sets with at least two pulse sequences yielding three images at each anatomical level: (1) TR = 0.3 sec, TE = 30 msec, (2) TR = 1.5, TE = 30, (3) TR = 1.5, TE = 120. Normal and pathological images have been analyzed using multispectral analysis and image classification. MR image data are first subjected to radiometric and geometric corrections to reduce error resulting from (1) instrumental variations in data acquisition, (2) image noise, and (3) misregistration. Training regions of interest (ROI) are outlined in areas of normal (gray and white matter, CSF) and pathological tissue. Statistics are extracted from these ROIs and classification maps generated using table lookup, minimum distance to means, maximum likelihood, and cluster analysis. These synthetic maps are then compared pixel by pixel with manually prepared classification maps of the same MR images. Using these methods, the authors have found that: (1) both supervised and unsupervised classification techniques yielded theme maps (class maps) which demonstrated tissue characteristic signatures and (2) tissue classification errors found in computer-generated theme maps were due to subtle gray scale changes present in the original MR data sets arising from radiometric inhomogeneity and spatial nonuniformity.

Brain↗
PubMed1986

Mixed-sclerosing-bone-dystrophy: 42-year follow-up of a case reported as osteopetrosis.

We present a detailed metabolic investigation and 42-year radiological follow-up of a 52-year-old man with mixed-sclerosing-bone-dystrophy, the rare occurrence of two or more distinct patterns of sclerosing-bone-dysplasia (e.g., osteopathia striata, osteopoikilosis, melorheostosis) in a single subject. Review of radiographs from 1942, when he was reported to have osteopetrosis, demonstrated diffuse osteosclerosis, osteopathia striata, osteopoikilosis, and focal cortical hyperostosis. Forty-two years later, there had been significant progression and evolution of his skeletal disease with the appearance of new areas of osteopathia striata and osteopoikilosis and a generalized increase in skeletal mass as assessed radiographically. Presence of subperiosteal bone apposition on biopsy of the iliac crest together with chronic mild hypocalcemia, secondary hyperparathyroidism, and hypophosphatemia suggested that enhanced bone formation, perhaps with defective skeletal resorption, is a fundamental abnormality which accounts for the increased bone mass of this patient.

Diagnostic Errors↗
PubMed1986

Strategies in the design of synthetic agonists and antagonists of growth hormone releasing factor.

Previous research on the favorable effects of mild conformational restriction in the N-terminal region of glucagon has led us to carry out analogue studies on the sequence-related 1-12 region of GRF(1-29)NH2. Replacement of each of the first 11 amino acids by its D-isomer in turn gave a total of 5 analogues exhibiting increases in potency. Other analogues containing multiple D-amino acid replacements were also examined and found to be highly potent, for instance: D-Tyr-1,D-Ala-2, 2630; His-1,D-Ala-2, 3440; Ac-His-1,D-Ala-2, 1574; D-Ala-2,Nle-27, 1840; D-Ala-2,D-Asn-8,Nle-27, 1580; D-Ala-2,D-Asp-3,D-Asn-8,Nle-27, 2000; D-Asp-3,D-Asn-8,Nle-27, 3810 (GRF(1-29) = 100%). It is possible that these results with D-isomers reflect the presence of reverse turns (beta-bends) in this region of GRF. Indeed, the qualitative predictive method of Chou and Fasman supports this theory and indicates reverse turns in the 1-5 and 6-10 sequences. Further studies were performed to test this hypothesis by introducing even more rigidity into the N-terminal region via disulfide bond formation between positions normally containing aromatic amino acids. None of the bridged peptides displayed biological activity which suggests that chain folding does not produce any proximity among N-terminal residues. We had shown previously that position 2(Ala) was extremely sensitive to both conformational and side-chain alterations. This observation was extended to analogues containing Sar and Pro, both of which were also inactive on GH release at the doses tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1986

Superactive amidated COOH-terminal glucagon analogues with no methionine or tryptophan.

The functions of the Trp-25 and Met-27 residues and the free carboxy terminus of glucagon have been debated for many years. Despite some semi-synthetic data to the contrary, comparison of the glucagon sequence with the other 5 members of this family of peptides, all of them amides and particularly growth hormone-releasing factor(1-29) amide and its recently described analogues, suggests that alterations to these positions should be quite well tolerated in terms of biological activity. To test this prediction, [Phe-25,Leu-27]-glucagon amide was synthesized in high yield and was found to actually have superior glycogenolytic activity (196%) to glucagon in the rat. Replacement of Gly-4 by D-Phe, which has been shown to give much enhanced glycogenolytic activity than glucagon itself, also increased the activity of [D-Phe-4,Phe-25,Leu-27]-glucagon amide (518%). The L-Phe-4-analogue, [Phe-4,25,Leu-27]-glucagon amide, in contrast, was 20 times less active (30%), strongly suggesting the presence of a beta-bend in this N-terminal region of glucagon. This was supported by Chou-Fasman structural predictions which indicate extensive folding in the 1-15 region. Indeed, additional conformational restriction by substitution of D-Ser in position 2 of glucagon also increased activity to 226%. [D-Gln-3]-glucagon was slightly less active (74%) than glucagon. Chou-Fasman calculations on glucagon were compared to similar treatments of the VIP, secretin, PHI, and GRF(1-29) sequences.

Amino Acid Sequence↗
PubMed1986

Oblique magnetic resonance imaging of the cardiovascular system.

This exhibit demonstrates that cardiac anatomy can be imaged by MRI in oblique planes that are equivalent to views obtained radiographically or at angiocardiography. These MR images may be obtained either by simple patient positioning or by electronic rotation of the imaging axis. The advantages of this technique include its simplicity and its ability to show detailed anatomy noninvasively. Major cardiac structures including chambers, walls, vessels and bronchi are optimally demonstrated in long axis or cross section. This permits estimation of chamber volume, wall thickness, vessel position and variations from normal. Smaller structures are also well visualized. These include the pericardium, papillary muscles, azygos vein and some cross sectional anatomy of the coronary arteries and veins. The valvular structures can be shown during diastole or systole. The ability of MRI to show these cardiac structures due to the intrinsic contrast differences in signal intensity between muscle, fat, flowing blood and lung suggest an important future for MR cardiac imaging in a broad group of congenital and acquired diseases of the heart, pericardium and great vessels.

Heart↗