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Biomedical subjects

C M Anderson

Publications and source records attributed to C M Anderson.

At least 91 records · Page 5Linked to original sources
PubMed1995

Assessment of carotid artery stenosis by ultrasonography, conventional angiography, and magnetic resonance angiography: correlation with ex vivo measurement of plaque stenosis.

PURPOSE: Several studies have investigated the correlation between Doppler ultrasonography (DUS), angiography (CA), and magnetic resonance angiography (MRA) in the evaluation of stenosis of the carotid bifurcation. However, these studies suffer from the lack of a true control-the lesion itself-and therefore conclusions about the diagnostic accuracy of each method remain relative. To determine the absolute accuracy of these modalities, we have prospectively studied lesion size with DUS, MRA, and CA in 28 patients undergoing 31 elective carotid endarterectomies and compared the percent of carotid stenosis determined by each technique to the carotid atheroma resected en bloc. METHODS: All patients were evaluated by each modality within 1 month before the thromboendarterectomy. With DUS, stenosis size was determined by standard flow criteria. For angiography and MRA, stenosis was defined as residual lumenal diameter/estimated normal arterial diameter (European Carotid Surgery Trial criteria). At surgery the carotid atheroma was removed en bloc in all patients. Patients in whom the lesion could not be removed successfully without damage were excluded from the study. Stenosis of the atheroma was determined ex vivo with high-resolution (0.03 mm3) magnetic resonance and confirmed by acrylic injection of the specimen under pressure and measurement of the atheroma wall and lumen. RESULTS: The measurements of the ex vivo stenosis by high-resolution magnetic resonance imaging correlated closely with the size of stenosis determined by the acrylic specimen casts (r = 0.92). By ex vivo measurement, the lesions were placed in the following size categories: 40% to 59% stenosis (n = 2), 60% to 79% stenosis (n = 6), 80% to 89% stenosis (n = 7), and 90% to 99% stenosis (n = 16). CONCLUSIONS: In general, the correlation of measurements of ex vivo stenosis with all modalities was good in these severely diseased arteries, although it was better for DUS (r = 0.80; p < 0.001) and MRA (r = 0.76; p < 0.001) than for CA (r = 0.56; p < 0.05).

Aged↗
PubMed1995

Anemia and insufficient milk in first-time mothers.

Insufficient milk is a poorly understood problem that is often identified as a major reason for early discontinuation of breastfeeding. This study explored the relationship between anemia and insufficient milk in 630 first-time mothers. The frequency of anemia (postpartum hemoglobin < 10 g/dL) was 22 percent. Anemic mothers reported a higher level of symptomatology associated with insufficient milk and were more frequently classified as having insufficient milk syndrome. Mothers with the syndrome reported a shorter period of full breastfeeding, and weaned at an earlier age. They identified not having enough milk, baby nursing too often, and baby not gaining enough weight as the main reasons for discontinuing breastfeeding, compared with baby's disinterest and conflicts with school or work as main reasons among mothers not reporting symptoms related to insufficient milk syndrome. The study results suggest that anemia is associated with the development of insufficient milk, which in turn, is related to duration of full breastfeeding and to age at weaning.

Adolescent↗
PubMed1995

Sodium chloride treatment of amphotericin B nephrotoxicity. Standard of care?

Amphotericin B is an effective therapeutic agent for most systemic or invasive mycoses, but its usefulness is limited by the frequent occurrence of nephrotoxicity. Given the high and increasing frequency of serious fungal infections, especially in immunocompromised patients, the importance of the morbidity caused by this toxicity is substantial. Salt loading may prevent and even reverse amphotericin B-induced azotemia by an unknown mechanism. A prospective, randomized, placebo-controlled trial in a relevant patient group would strengthen the support for this simple, safe therapy, but will not likely be carried out because of practical and ethical considerations. Thus, a few prospective and limited controlled human studies may be the only supportive evidence for using this therapy. Supplementing dietary sodium chloride intake with 150 mEq of sodium chloride daily intravenously or orally beginning when or before amphotericin B therapy is initiated will likely prevent much of the observed nephrotoxicity and should be carried out routinely.

Amphotericin B↗
PubMed1995

Systemic treatments for advanced cutaneous melanoma.

The treatment of advanced cutaneous melanoma remains disappointing. Single-agent cytotoxic drugs usually produce response rates of less than 20%, though newer agents, particularly fotemustine and temozolomide, show some promise, especially in patients with brain metastases. Combination chemotherapy regimens yield response rates of 20% to 40%, but durable complete remissions are uncommon. Interferon-alfa and interleukin-2 alone produce response rates of 10% to 20%, 3% to 5% of which are durable. Vaccines and monoclonal antibodies have low level activity in advanced disease but may play a role in the adjuvant setting. The combinations of cisplatin-based regimens plus IFN-alfa and IL-2 have produced overall response rates of 50% to 60% and complete responses in 20% of patients, about half of which are durable. The toxicity of these regimens is severe, however, and their impact on survival remains to be established.

Antibodies, Monoclonal↗
PubMed1994

Interleukin-1 beta induces cytosolic phospholipase A2 and prostaglandin H synthase in rheumatoid synovial fibroblasts. Evidence for their roles in the production of prostaglandin E2.

OBJECTIVE: In order to investigate potential regulatory mechanisms for the increased production of prostaglandin E2 (PGE2) in interleukin-1 beta (IL-1 beta)-stimulated rheumatoid synovial fibroblasts (RSF), this study examined the induction of phospholipase A2 (PLA2) and prostaglandin H synthase (PGHS) enzymes and the correlation of these events with PGE2 production in IL-1 beta-stimulated RSF. METHODS: Protein and messenger RNA (mRNA) levels of cytosolic PLA2 (cPLA2) and PGHS-2 enzymes in IL-1 beta-stimulated RSF were measured by Western and Northern blotting, respectively, using specific antisera and complementary DNA probes. Enzymatic activity of cPLA2 was determined in cell-free reaction mixtures utilizing mixed micelles of 14C-phosphatidylcholine and Triton X-100 as the substrate. PGE2 levels were quantitated using a commercial enzyme immunoassay kit. RESULTS: Incubation of RSF with IL-1 beta increased the mRNA and protein levels for the high molecular weight cPLA2 as well as for the mitogen/growth factor-responsive PGHS (PGHS-2). The IL-1 receptor antagonist completely abolished the induction of these two enzymes and the stimulation of PGE2 production by IL-1 beta in RSF. In contrast, levels of the other known forms of these enzymes, i.e., the 14-kd secretory group II PLA2 (sPLA2) and the constitutive form of PGHS (PGHS-1), were unaffected by IL-1 beta treatment. CONCLUSION: These are the first data to demonstrate the coordinate induction by IL-1 of cPLA2 and PGHS-2 in RSF. The time-course for the induction of these enzymes suggests that their increase contributes to the increased production of PGE2 in IL-1-treated RSF, and may help explain the capacity of RSF to produce large amounts of PGE2.

Arthritis, Rheumatoid↗
PubMed1994

MRA studies of arterial stenosis: improvements by diastolic acquisition.

Cardiac-phase-specific data acquisition is used to reduce signal loss in MR Angiography resulting from disturbed flow. RF pulses are delivered continuously throughout the cardiac cycle, but incrementation of phase-encoding gradients and data storage are enabled only during the chosen part of the cycle. Studies in a stenotic pulsatile flow phantom demonstrate that poststenotic signal loss is primarily determined by the mean flow velocity, and is not appreciably affected by acceleration or deceleration of the mean flow rate. The signal loss is least in diastole. In vivo studies in patients with carotid artery disease show that data acquisition in diastole reduces the apparent degree and extent of carotid bifurcation stenosis and provides a crisper definition of the vascular lumen. The additional time required for cardiac-phase-specific acquisition can be reduced by gating only the lower-order phase-encoding lines while retaining acceptable image quality.

Blood Flow Velocity↗
PubMed1994

MR gradient echo imaging of intravascular blood oxygenation: T2* determination in the presence of flow.

The T2* relaxation time of blood varies with its oxygen saturation. To evaluate the feasibility of imaging intravascular blood oxygenation in humans using a conventional 1.5T MR system, we have implemented a method to measure T2* of blood despite the presence of pulsatile flow. The method was tested in a) stationary and flow phantoms, b) blood samples at different levels of oxygen saturation, and c) a human hypoxia model. Our results demonstrate the ability of cardiac-triggered, flow compensated gradient echo imaging to obtain reproducible T2* measurements of flowing blood in vivo.

Artifacts↗
PubMed1994

High speed bolus tagging: time resolved velocity quantification of pulsatile flow in a single breath hold.

We have implemented a high speed method for cardiac-triggered blood velocity quantification within a single breath hold on a conventional MR system. The method, based on bolus tagging, was tested using a pulsatile flow phantom and evaluated in vivo. The image acquisition time was reduced by a factor of N by acquiring N phase encode lines per bolus tag application. The clarity of the flow tag was found to vary with how k-space was covered during data collection. The technique was optimized and multiple bolus tag images were obtained throughout the cardiac cycle within a single breathold.

Aorta, Thoracic↗
PubMed1994

Analysis of receptor clustering on cell surfaces by imaging fluorescent particles.

Fluorescently labeled low density lipoproteins (LDL) and influenza virus particles were bound to the surface of human fibroblasts and imaged with a cooled slow-scan CCD camera attached to a fluorescence microscope. Particles were also imaged after attachment to polylysine-coated microscope slides. The digital images were analyzed by fitting data points in the region of fluorescent spots by a two-dimensional Gaussian function, thus obtaining a measure of spot intensity with correction for local background. The intensity distributions for particles bound to polylysine slides were mainly accounted for by particle size distributions as determined by electron microscopy. In the case of LDL, the intensity distributions for particles bound to fibroblasts were considerably broadened, indicative of clustering. The on-cell intensity distributions were deconvolved into 1-particle, 2-particle, 3-particle, etc. components using the data obtained with LDL bound to polylysine-coated slides as an empirical measure of the single particle intensity distribution. This procedure yielded a reasonably accurate measure of the proportion of single particles, but large errors were encountered in the proportions of larger cluster sizes. The possibility of studying the dynamics of clustering was investigated by binding LDL to cells at 4 degrees C and observing changes in the intensity distribution with time after warming to 20 degrees C.

Biophysical Phenomena↗
PubMed1994

Bilateral fatigue fractures of the radial shaft in a gymnast.

A 24-year-old female gymnast had a 3-month history of bilateral forearm pain. A Tc-99m MDP bone scan demonstrated focally increased activity in the radial shafts on blood pool and delayed images, characteristic of fatigue fractures. Fatigue fractures commonly occur in the lower extremities. Upper extremity fatigue fractures, in contrast, are uncommon and usually involve the humerus or ulna. Fatigue fracture of the radial shaft from gymnastic exercise has not been previously reported.

Adult↗
PubMed1994

Measurement of internal carotid artery stenosis from source MR angiograms.

PURPOSE: To determine whether interpretation of internal carotid artery (ICA) stenosis from source partitions is more accurate than interpretation from maximum-intensity projections (MIPs) from three-dimensional (3D) time-of-flight (TOF) magnetic resonance (MR) angiography. MATERIALS AND METHODS: The percentage of diameter ICA stenosis was measured on source images and MIPs from sagittal (n = 150) and transverse (n = 140) 3D TOF MR angiography. Measurements were compared with those from conventional angiography. RESULTS: Sensitivity and specificity for distinguishing 70%-99% stenosis were 96% and 78%, respectively, for sagittal MIPs, 88% and 90% for sagittal source images, 92% and 86% for transverse MIPs, and 92% and 95% for transverse source images. Areas under the receiver operating characteristic curves statistically significantly increased (P < .05) with interpretation from source images. Complete loss of intravascular signal was not encountered on source partitions except within a greater than 85% stenosis. CONCLUSION: Interpretation of source partitions rather than MIPs reduces the tendency for overestimation of stenosis with MR angiography and improves the specificity for discriminating 70%-99% stenosis.

Aged↗
PubMed1993

Transmembrane signaling by an insulin receptor lacking a cytoplasmic beta-subunit domain.

To assess the function of the cytoplasmic domain of the insulin receptor (IR) beta subunit, we have studied a mutant IR truncated by 365 aa (HIR delta 978), thereby deleting > 90% of the cytoplasmic domain. HIR delta 978 receptors were processed normally to homodimers that were expressed at the cell surface where they bind insulin with normal affinity. Although these truncated IRs were inactive with respect to ligand-induced internalization and autophosphorylation, insulin stimulated endogenous substrate (pp185) phosphorylation significantly more in HIR delta 978 cells than in untransfected Rat1 cells. Importantly, despite absence of the beta-subunit cytoplasmic domain, fibroblasts expressing HIR delta 978 receptors displayed enhanced sensitivity to insulin for stimulation of glucose incorporation into glycogen, alpha-aminoisobutyric acid uptake, thymidine incorporation, and S6 kinase activity compared with parental fibroblasts. Insulin also induced the expression of the protooncogene c-fos and the early growth response gene Egr-1 in HIR delta 978 cells far greater than in parental Rat1 fibroblasts. Furthermore, an agonistic monoclonal antibody specific for the human IR stimulated insulin action in fibroblasts expressing wild-type human IR but had no effect on HIR delta 978 cells. In conclusion, the HIR delta 978 truncated IRs appear to confer enhanced insulin sensitivity by augmenting the signaling properties of the endogenous rodent IRs.

Aminoisobutyric Acids↗
PubMed1993

Recombinant human type II phospholipase A2 lacks edema producing activity in rat.

The rat paw edema-inducing, acute inflammatory activity of four snake venom phospholipase A2S (PLA2) (Naja naja, Naja mocambique mocambique, Crotalus atrox and recombinant Naja naja naja) and of recombinant human type II PLA2 (rh-PLA2) found in rheumatoid synovial fluid, were compared after a bolus subplantar injection. The snake venom-derived PLA2s, including the recombinant Naja naja naja, were potent inducers of paw edema. On the other hand, when given in similar amounts (protein and/or enzymatic activity), the rh-PLA2 did not produce paw edema. Furthermore, the addition of Naja naja PLA2, blood plasma from rats with adjuvant arthritis or the E. coli-based enzymatic incubation mixture used to measure PLA2 activity to the injection mixture containing rh-PLA2, did not result in paw edema-inducing activity. These results suggest that the lack of paw edema-inducing activity of rh-PLA2 may be due to significant structural differences between snake venom PLA2s and human PLA2 which allow snake venom PLA2s, but not the human group II PLA2, to express inflammatory activity as measured by paw edema in rat induced by a bolus injection.

Animals↗
PubMed1993

Interleukin-1 beta induces cytosolic PLA2 in parallel with prostaglandin E2 in rheumatoid synovial fibroblasts.

We investigated the temporal relationship between the increase in enzymatic activity and protein of a high molecular weight (100 kDa), cytosolic PLA2 (cPLA2) in interleukin-1 beta (IL-1 beta)-treated rheumatoid synovial fibroblasts (RSF). Both of these responses increased according to a similar time-course which correlates with PGE2 production by these cells. In contrast, 14 kDa, secreted PLA2 (sPLA2), which was also produced by RSF, was not affected by IL-1 beta treatment. These findings support that an augmentation of CPLA2 activity, caused by an induction of cPLA2 protein, rather than sPLA2, is temporally associated with increased PGE2 production in IL-1 beta-treated RSF.

Arthritis, Rheumatoid↗
PubMed1993

Relative expression of insulin receptor isoforms does not differ in lean, obese, and noninsulin-dependent diabetes mellitus subjects.

The insulin receptor is expressed as two isoforms that differ by a 12-amino acid region at the carboxy-terminus of the alpha-subunit encoded by exon 11. These isoforms are produced by tissue-specific alternate splicing of the insulin receptor mRNA. To determine whether the relative expression of the isoforms is altered in skeletal muscle in two insulin-resistant states, NIDDM and obesity, relative mRNA levels were measured using a polymerase chain reaction technique. There were no differences in the relative amounts of skeletal muscle mRNA encoding the exon 11-containing form compared to the exon 11-lacking form of the insulin receptor among lean normal (30 +/- 2% Ex11-), obese nondiabetic (32 +/- 2%), and NIDDM (31 +/- 1%) subjects. We conclude that altered expression of insulin receptor isoform mRNAs does not account for skeletal muscle insulin resistance in NIDDM and obesity.

Adult↗