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Biomedical subjects

M Sanders

Publications and source records attributed to M Sanders.

At least 73 records · Page 4Linked to original sources

Safety of unilateral and bilateral percutaneous cervical cordotomy in 80 terminally ill cancer patients.

PURPOSE AND METHODS: The safety of percutaneous cervical cordotomy (PCC) and bilateral percutaneous cervical cordotomy (BPCC) was studied in 62 and 18 patients, respectively, with intractable malignant pain. Cordotomy was indicated for pain that did not respond to any other therapy. RESULTS: After PCC, 54 patients showed satisfactory, six partial, and two no pain relief. Concerning major permanent complications, urinary retention, hemiparesis, and mirror-image pain occurred in four (6.5%), five (8.1%), and four (6.5%) patients, respectively. After BPCC, nine patients showed satisfactory, six partial, and three no pain relief. The major permanent complications were the same as after PCC, and occurred in two (11.1%), two (11.1%), and one (5.6%) patient, respectively. Sleep-induced apnea was not observed in any patient. CONCLUSION: In the treatment of intractable malignant pain, localized unilaterally, if other symptomatic management fails, PCC is a recommendable procedure, particularly when pain due to movement dominates. However, due to the high incidence of complications combined with the high failure rate, BPCC is not recommended.

Adult↗

beta-Scruin, a homologue of the actin crosslinking protein scruin, is localized to the acrosomal vesicle of Limulus sperm.

Scruin (alpha-scruin) is an actin bundling protein found in the acrosomal process of Limulus polyhemus sperm. We have cloned and sequenced a second scruin isoform from Limulus, beta-scruin, that is 67% identical to alpha-scruin. Northern and Southern analyses confirm that beta-scruin and alpha-scruin are encoded by distinct genes. The sequence of beta-scruin, like alpha-scruin, is organized into N- and C-terminal superbarrel domains that are characterized by a six-fold repeat of a 50 residue motif. Western analysis using rabbit polyclonal antisera specific for alpha- and beta-scruin indicate that beta-scruin, like alpha-scruin, is found in Limulus sperm but not blood or muscle. Both immunofluorescence microscopy and immunogold-EM localize beta-scruin within the acrosomal vesicle at the anterior of sperm but not in the acrosomal process. The function of beta-scruin in this membrane-bounded compartment that is devoid of actin is unknown. However, the location of beta-scruin together with the fact that it contains two putative beta-superbarrel structural folds, which are known to be catalytic domains in a number of proteins, suggests it may have a possible enzymatic role.

Acrosome↗

Molecular and cellular concepts in atherosclerosis.

Atherosclerosis is a complex disease of uncertain cause. Its pathobiology is believed to represent an abnormal expression of the processes of vascular healing. Etiologic models derive from a 'response to injury' paradigm and can be divided into three separate disease stages: endothelial dysfunction, smooth muscle proliferation and architectural disruption. The initiating event of endothelial dysfunction is unknown, but is believed to be related to low-density lipoproteins and/or their oxidized derivatives. Endothelial injury is signalled to the smooth muscle cells of the media by three routes: direct cell-cell interaction, secretion of soluble growth factors and monocyte-derived cytokines. Monocytes are recruited by the endothelium and invade the subintimal space by a complex interaction of a variety of adhesion proteins and receptors on both cell types. Smooth muscle cell proliferation is initiated by a change in phenotype expression from 'contractile' to 'synthetic' resulting from the binding of fibronectin to specific integrin receptors. Three functionally distinct activities may represent separate subtypes of the 'synthetic phenotype': migration from the media to the intima, increased proliferation and inappropriate extracellular matrix synthesis. The loss of normal regulatory control and anchorage independence of proliferation suggest a relationship to oncogenic transformation. Both migration and proliferation result from the binding of platelet-derived growth factor-like factors to smooth muscle cell receptors, which initiates a cascade of intracellular molecular events leading either to cytoskeletal locomotory restructuring or cell cycle activation. Both pathways also appear to be coregulated by integrin receptors and both depend upon phosphorylation of cell membrane, cytosolic and nuclear regulatory proteins. Clinical expression of atherosclerosis may follow sudden loss of architectural integrity of the intimal plaque by three different mechanisms: plaque fissuring, intraluminal plaque rupture or intramural hemorrhage related to abnormal vessel wall stress and/or biochemistry.

Animals↗

Portable recording in the assessment of obstructive sleep apnea. ASDA standards of practice.

The objective assessment of patients with a presumptive diagnosis of obstructive sleep apnea (OSA) has primarily used attended polysomnographic study. Recent technologic advances and issues of availability, convenience and cost have led to a rapid increase in the use of portable recording devices. However, limited scientific information has been published regarding the evaluation of the efficacy, accuracy, validity, utility, cost effectiveness and limitations of this portable equipment. Attaining a clear assessment of the role of portable devices is complicated by the multiplicity of recording systems and the variability of clinical settings in which they have been analyzed. This paper reviews the current knowledge base regarding portable recording in the assessment of OSA, including technical considerations, validation studies, potential advantages and disadvantages, issues of safety, current clinical usage and areas most in need of further study.

Ambulatory Care↗

Vasopressin receptor-mediated endocytosis in cells transfected with V1-type vasopressin receptors.

We examined the process of receptor-mediated endocytosis in A-9 lung fibroblast and chinese hamster ovary (CHO) cells transfected with the recently cloned vasopressin V1a receptor (51). We used a fluorescent labeled vasopressin analog (rhodamine-mercaptopropionic acid lysine vasopressin) and radiolabeled vasopressin to examine this process in the two transfected cell lines. Both A-9 and CHO cells internalize vasopressin in a manner consistent with receptor-mediated endocytosis. A-9 cells internalize vasopressin more rapidly than CHO cells. The process is inhibited by vasopressin and by specific vasopressin V1 receptor antagonists but not by specific V2 receptor antagonists. Hypertonic sucrose inhibits endocytosis in both cell types suggesting a role of clathrin coated pits in the endocytosis of receptor in these cells. These cells are excellent models in which to examine the effect of receptor mutations on vasopressin receptor-mediated endocytosis.

Animals↗

Beam profile analysis using GafChromic films.

GafChromic film dosimetry techniques were used to evaluate the beam profiles for each collimator of the Leksell Gamma Knife at the University of Kentucky Medical Center. At the conclusion of acceptance testing, representatives from Leksell exposed conventional films for beam profile processing and analysis in Sweden. At the same time, an inhouse technique using GafChromic films was utilized in the analysis of the beam profiles. GafChromic films were irradiated to 100 Gray to provide data in each of the three planes for each collimator size. The films were analyzed using a scanning helium-neon laser densitometer with a small aperture of 5-10 microns. The digitized density profiles were curve-fitted using a PC plotting algorithm. The curve-fitted density profiles were converted to relative dose using a standard calibration curve determined with a conventional cobalt-60 teletherapy beam. The results are in excellent agreement with the conventional film analysis reported by Leksell. The GafChromic method has proven to be an accurate and rapid method of analysis and could be easily incorporated into a quality assurance program.

Calibration↗

A tissue equivalent phantom for stereotactic radiosurgery localization and dose verification.

A tissue equivalent head phantom was utilized in the stereotactic localization and dose verification of radiosurgery procedures with the Leksell Gamma Knife Unit at the University of Kentucky Medical Center. A radiation dose-dependent color-doped gel target was positioned within the head phantom and stereotactically localized using either angiography, CT, or MR techniques. Utilizing standard Gamma Knife treatment procedures, the head phantom was irradiated, which resulted in a color change of the gel tumor at the position of the treatment isocenter and thereby confirmed the localization procedure. Additionally, a radiation dosimeter (thermoluminescent dosimetry--TLD) was positioned within the head phantom and localized using an angiography frame and a standard radiation therapy simulator. The phantom skull measurements and the dosimeter coordinates were entered into the Leksell Gamma Knife dose planning computer (KULA) and an irradiation time for 40 Gy using the 18-mm collimator was determined. The TLD dose evaluations were relatively determined using a cobalt-60 calibration curve. The experimental dose verification results agreed well (+/- 4%) with computer dose estimates.

Algorithms↗

American Orthopaedic Foot and Ankle Society women's shoe survey.

Shoes have been implicated as being responsible for the majority of foot deformities and problems that physicians encounter in women. A total of 356 women were studied in this investigation to evaluate trends in women's shoe wear and their effect on the development of foot deformities and pain. The majority of women in this study wore shoes that were too small for their feet, had foot pain and deformity, and had increased shoe size since the age of 20. Few women had their feet measured in over 5 years. The women without foot pain or deformities also wore shoes that were smaller than their feet but to a lesser degree.

Adult↗

Insulin-like growth factors stimulate erythropoiesis in serum-substituted umbilical cord blood cultures.

The stimulatory effects of the insulin-like growth factors (IGFs) on erythroid colony formation by hematopoietic progenitor cells derived from adult bone marrow and peripheral blood have been well demonstrated. To enhance our understanding of the potential role of IGFs in human newborn erythropoiesis, we studied the effects of IGF-I and IGF-II on neonatal erythropoiesis in vitro. Erythroid progenitor cells were recovered from umbilical cord blood collected at scheduled Cesarean sections from women with term, uncomplicated pregnancies. Light-density cord blood mononuclear cells were cultured for 7 days in a serum-substituted culture system supplemented with and without purified human recombinant erythropoietin (0.5 to 2.0 U/mL) and recombinant human IGFs. Addition of IGF-I (1 to 100 ng/mL) resulted in up to a 4-fold increase over baseline erythropoietin-dependent colony formation at 7 days with a maximal effect at 10 ng/mL. While subphysiologic doses of IGF-II caused a modest stimulation of erythropoiesis, addition of a physiologic concentration (100 ng/mL) resulted in up to a 4-fold enhancement in erythroid colony formation. This stimulatory effect persisted in cultures of mononuclear cells that were depleted of monocytes, myeloid cells, T cells and B cells prior to culture, suggesting that enhancement is the result of a direct IGF effect on progenitor cells. Addition of IGFs in the absence of erythropoietin resulted in erythroid colony formation in some but not all experiments. Whereas IGF-I was the primary regulator of erythropoietin-independent erythroid colony formation by adult erythroid progenitors, IGF-II was the predominant regulator of erythropoietin-independent erythroid colony formation by neonatal progenitor cells. We conclude that IGFs in physiologic doses directly stimulate neonatal cord blood erythroid progenitor cells and may play a role in developmental control of human erythropoiesis.

Blood↗

Antibody affinity to retinal S-antigen in patients with retinal vasculitis.

Using a modified enzyme-linked immunosorbent antibody method that included dissociation of antigen antibody complexes with sodium thiocyanate, we examined the functional affinity of antibody to retinal S-antigen in 48 patients with retinal vasculitis and 46 age-matched healthy control subjects. Antibody affinity was markedly lower in patients with retinal vasculitis than in healthy subjects. Low-affinity antibody was more prevalent in acute retinal vasculitis and in patients with normal levels of circulating immune complexes. We found distinct differences between the antiretinal antibodies found in patients with retinal vasculitis and those in control subjects. The association of low-affinity antibody with normal levels of circulating immune complexes may suggest defective regulation of antiretinal autoimmunity and have important pathogenic implications.

Antibody Affinity↗

A vasopressin analog that binds but does not activate V1 or V2 vasopressin receptors is not internalized into cells that express V1 or V2 receptors.

To assess whether receptor binding is sufficient to initiate vasopressin receptor endocytosis in cells expressing the vasopressin V1 or V2 receptors, we synthesized a novel fluorescent-labeled vasopressin analog, [1-(beta-mercapto-beta, beta-cyclopentamethylene propionic acid), 2-(O-ethyl)-D-tyrosine, 4-valine, 8-lysine-N6-carboxytetramethylrhodamine] vasopressin (R-CLVP), that binds to vasopressin receptors but does not activate intracellular events such as the mobilization of intracellular calcium or the activation of adenylate cyclase. We compared the manner in which this analog was endocytosed in cells expressing V1 (A-10, rat smooth muscle cells) or V2 (LLC-PK1, porcine kidney cells) receptors with that of a full agonist, [1-(beta-mercaptopropionic acid), 8-lysine-N6-carboxytetramethylrhodamine] vasopressin (R-MLVP) [Lutz et al. (1990) J. Biol. Chem. 265, 4657-4663; Lutz et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87,6507-6511]. We showed that R-CLVP bound to both types of receptors with good affinity. It failed to increase cyclic AMP concentrations in LLC-PK1 cells and did not increase the mobilization of intracellular calcium in A-10 cells. It bound to the surface of both these cell types in a diffuse manner and it did not undergo receptor endocytosis in either cell type. In contrast, R-MLVP, an agonist that bound to both receptor subtypes and elicited changes in intracellular cyclic AMP and calcium, bound to the surface of these cells in a diffuse manner at early times after exposure, and rapidly underwent endocytosis. We conclude that binding of vasopressin to its receptors alone is insufficient to cause receptor endocytosis, and other events distal to the receptor are required to initiate endocytosis. R-CLVP should be a useful analog in determining the factors responsible for initiating receptor endocytosis.

Amino Acid Sequence↗

The identification of the Bs breakpoint and of two possible Bar genes.

Two coding regions were identified within a 110 kb region which includes all mapped Bar breakpoints. Both lie proximal to the identified Bar breakpoints. The first coding region, designated BarA, is 5 kb from the most proximal Bar mutation, B581, and 66 kb from the Bs breakpoint. It encodes a 1.3 kb transcript, which is found in late third instar larvae but is absent in 1-3-day-old pupae. Bi, R(B)hd3, B85c15, and Bs result in overproduction of this transcript in late third instar larvae. A second coding region, which was previously identified as BarH1, maps 18 kb from B581 and 79 kb from the Bs breakpoint. In third instar larvae, the abundance of the BarH1 transcript is very low in both wild type and various Bar mutatants, with the exception of R(B)hd3. In 1-3-day-old pupae, the level of the BarH1 transcript is higher. BarH1 was previously identified as the Bar gene. However, this report raises the possibility that BarA rather than BarH1 is the Bar gene or that more than one gene may be involved in Bar position effects.

Animals↗