A different view of "Toc", as I knew him.
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Biomedical Research↗
Biomedical subjects
D Green
Publications and source records attributed to D Green.
Natural marine sponge fiber skeleton: a biomimetic scaffold for human osteoprogenitor cell attachment, growth, and differentiation.
Identification of suitable scaffolds onto which human stem cells can be seeded to generate functional three-dimensional tissues is a major research goal. A natural marine sponge skeleton was selected as a potential scaffold on the basis of the hydration potential of the fiber, the presence of open interconnected channels created by the fiber network, the collagenous composition of the fiber, and the structural diversity of fiber architecture. The skeleton of an undetermined species of Spongia (Class Demospongiae: Order Dictyoceratida: Family Spongiidae), composed of spongin, supported growth of human osteoprogenitor cells. Cell attachment and invasion into the framework were observed within 16 h, followed by development into membranous sheets between the sponge fibers by concentric infilling. Histochemical staining for alkaline phosphatase and type I collagen indicated formation of bone matrix as confirmed by birefringence. At 9 and 14 days alkaline phosphatase-specific activity in sponge fiber-osteoprogenitor cell cultures was significantly greater than in control cultures on cell culture plastic. Adsorption with recombinant human bone morphogenetic protein 2 confirmed the potential of this sponge skeleton as a delivery scaffold for osteogenic factors. The abundance and structural diversity of natural marine sponge skeletons and their potential as multifunctional, cell conductive and inductive frameworks indicate a promising new source of scaffold for tissue regeneration.
Animals↗
Coagulation changes in individuals with sickle cell trait.
Sickle cell disorders, such as Hb SS and Hb SC, are associated with a hypercoagulable state that may contribute to the vaso-occlusive episodes observed in the disorders. To what extent increased coagulation activity occurs in individuals with sickle cell trait has had limited study. Because such information may help clarify clinical and pathologic findings that may occur in these individuals and may be useful in clarifying the hypercoagulable state in sickle cell disease, we have examined individuals with Hb AS to determine the extent that increased coagulation activity does occur. We measured d-dimers, thrombin-antithrombin (TAT) complexes, prothrombin fragment 1.2 (F1.2), absolute blood monocyte levels, proteins C and S, and isotypes of antiphospholipid antibodies in individuals with Hb AS and in matched controls (Hb AA). Results showed that d-dimers, TAT, and F1.2 were increased significantly above normal levels. Absolute blood monocyte levels were increased. The d-dimers, TAT, F1.2, and monocyte counts showed significant increasing trends through groups of increasing severity (Hb AA, Hb AS, Hb SC, and Hb SS). Our study shows that individuals with Hb AS have increased coagulation activity, with d-dimers, TAT, and F1.2 being consistent indicators. The measures of coagulation activity in Hb AS are lower than in patients with Hb SC and Hb SS disease. These results extend our previous observation that the degree of coagulation activation parallels the degree of disease severity among sickle cell genotypes. The findings suggest that monocytosis, with the possible expression of monocyte-derived tissue factor, and the associated hypercoagulable state are driven by disease severity.
Adult↗
The potential of biomimesis in bone tissue engineering: lessons from the design and synthesis of invertebrate skeletons.
Synthetic bone replacement materials are now widely used in orthopedics. However, to date, replication of trabecular bone structure and mechanical competence has proved elusive. Maximization of bone tissue attachment to replacement materials requires a highly organized porous structure for tissue integration and a template for assembly, combined with structural properties analogous to living bone. Natural structural biomaterials provide an abundant source of novel bone replacements. Animal skeletons have been designed through optimization by natural selection to physically support and physiologically maintain diverse tissue types encompassing a variety of functions. These skeletons possess structural properties that provide support for the complete reconstruction and regeneration of ectodermal, mesodermal, and bone tissues derived from animal and human and are thus suited to a diversity of tissue engineering applications. Increased understanding of biomineralization has initiated developments in biomimetic synthesis with the generation of synthetic biomimetic materials fabricated according to biological principles and processes of self-assembly and self-organization. The synthesis of complex inorganic forms, which mimic natural structures, offers exciting avenues for the chemical construction of macrostructures and a new generation of biologically and structurally related bone analogs for tissue engineering.
Animals↗
Persistent post-sclerotherapy pigmentation due to minocycline. Three cases and a review of post-sclerotherapy pigmentation.
BACKGROUND: Post-sclerotherapy pigmentation, usually overlying the treated veins and independent of any drug ingestion, is common. This pigmentation is brown and represents haemosiderin and sometimes melanin as well. It usually slowly fades over a period of months, only uncommonly persisting for years. Cutaneous pigmentation due to minocycline ingestion is a known but rare adverse effect. It usually appears as a round or irregular shaped patch that is dark blue to black, representing minocycline moieties and iron complexes. Its persistence for years is common. Clinically and histopathologically, these two causes of pigmentation are quite distinct. In the absence of ulceration, minocycline pigmentation koebnerised by sclerotherapy has not previously been reported. AIMS: To determine the nature of the pigmentation appearing in three patients who had been taking minocycline at the time, or shortly after, they had received sclerotherapy. Clinically, although this pigmentation had the usual distribution observed after sclerotherapy, it was persistent and appeared dark blue to black. RESULTS: The persistent post-sclerotherapy linear pigmentation observed in all three patients had the characteistics of minocycline pigmentation. CONCLUSIONS: This is the first report of such minocycline-aggravated post-sclerotherapy pigmentation. Persistent post-sclerotherapy pigmentation caused by minocycline is a risk associated with ingestion of this drug. Patients need to be warned of this risk because, unlike post-sclerotherapy pigmentation that develops in the absence of drug ingestion, minocycline-aggravated post-sclerotherapy pigmentation may persist for years.
Adult↗
Biogeography and ecological setting of Indian Ocean hydrothermal vents.
Within the endemic invertebrate faunas of hydrothermal vents, five biogeographic provinces are recognized. Invertebrates at two Indian Ocean vent fields (Kairei and Edmond) belong to a sixth province, despite ecological settings and invertebrate-bacterial symbioses similar to those of both western Pacific and Atlantic vents. Most organisms found at these Indian Ocean vent fields have evolutionary affinities with western Pacific vent faunas, but a shrimp that ecologically dominates Indian Ocean vents closely resembles its Mid-Atlantic counterpart. These findings contribute to a global assessment of the biogeography of chemosynthetic faunas and indicate that the Indian Ocean vent community follows asymmetric assembly rules biased toward Pacific evolutionary alliances.
Animals↗
Genetic hypercoagulability: screening should be an informed choice.
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Decision Making↗
Structure-based design, synthesis and SAR of a novel series of thiopheneamidine urokinase plasminogen activator inhibitors.
The serine protease urokinase plasminogen activator (uPA) is thought to play a central role in tumor metastasis and angiogenesis. Molecular modeling studies suggest that 5-thiomethylthiopheneamidine inhibits uPA by binding at the S1 pocket of the active site. Further structure based elaboration of this residue resulted in a novel class of potent and selective inhibitors of uPA.
Antimetabolites↗
Synthesis of thiophene-2-carboxamidines containing 2-aminothiazoles and their biological evaluation as urokinase inhibitors.
The serine protease urokinase (uPa) has been implicated in the progression of both breast and prostate cancer. Utilizing structure based design, the synthesis of a series of substituted 4-[2-amino-1,3-thiazolyl]-thiophene-2-carboxamidines is described. Further optimization of this series by substitution of the terminal amine yielded urokinase inhibitors with excellent activities.
Amidines↗
Structural determinants for activation or inhibition of ryanodine receptors by basic residues in the dihydropyridine receptor II-III loop.
The structures of peptide A, and six other 7-20 amino acid peptides corresponding to sequences in the A region (Thr671- Leu690) of the skeletal muscle dihydropyridine receptor II-III loop have been examined, and are correlated with the ability of the peptides to activate or inhibit skeletal ryanodine receptor calcium release channels. The peptides adopted either random coil or nascent helix-like structures, which depended upon the polarity of the terminal residues as well as the presence and ionisation state of two glutamate residues. Enhanced activation of Ca2+ release from sarcoplasmic reticulum, and activation of current flow through single ryanodine receptor channels (at -40 mV), was seen with peptides containing the basic residues 681Arg Lys Arg Arg Lys685, and was strongest when the residues were a part of an alpha-helix. Inhibition of channels (at +40 mV) was also seen with peptides containing the five positively charged residues, but was not enhanced in helical peptides. These results confirm the hypothesis that activation of ryanodine receptor channels by the II-III loop peptides requires both the basic residues and their participation in helical structure, and show for the first time that inhibition requires the basic residues, but is not structure-dependent. These findings imply that activation and inhibition result from peptide binding to separate sites on the ryanodine receptor.
Amino Acid Sequence↗
Removal of periocular veins by sclerotherapy.
PURPOSE: Prominent periocular veins, especially of the lower eyelid, are not uncommon and patients often seek their removal. Sclerotherapy is a procedure that has been successfully used to permanently remove varicose and telangiectatic veins of the lower extremity and less frequently at other sites. Although it has been successfully used to remove dilated facial veins, it is seldom performed and often not recommended in the periocular region for fear of complications occurring in adjacent structures. The purpose of this study was to determine whether sclerotherapy could safely and effectively eradicate prominent periocular veins. DESIGN: Noncomparative case series. PARTICIPANTS: Fifty adult female patients with prominent periocular veins in the lower eyelid were treated unilaterally. PATIENTS AND METHODS: Sclerotherapy was performed with a 0.75% solution of sodium tetradecyl sulfate. All patients were followed for at least 12 months after treatment. MAIN OUTCOME MEASURES: Complete clinical disappearance of the treated vein was the criterion for success. RESULTS: All 50 patients were successfully treated with uneventful resorption of their ectatic periocular veins. No patient required a second treatment and there was no evidence of treatment failure at 12 months. No new veins developed at the treated sites and no patient experienced any ophthalmologic or neurologic side effects or complications. CONCLUSIONS: Sclerotherapy appears to be a safe and effective means of permanently eradicating periocular veins.
Adult↗
The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes.
OBJECTIVES: The purpose of this study was to examine whether exercise training stimulates a generalized improvement in vascular function in patients with type 2 diabetes mellitus. BACKGROUND: Exercise is often recommended for patients with type 2 diabetes to improve physical conditioning and glycemic control. This study examined the effect of eight weeks of exercise training on conduit and resistance vessel function in patients with type 2 diabetes, using a randomized crossover design. METHODS: Both resistance vessel endothelium-dependent and -independent functions were determined by forearm plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in 16 patients with type 2 diabetes. Conduit vessel endothelial function was assessed in 15 of these patients using high-resolution ultrasound and flow-mediated dilation of the brachial artery; glyceryl trinitrate (GTN) was used as an endothelium-independent dilator. RESULTS: Flow-mediated dilation increased from 1.7 +/- 0.5% to 5.0 +/- 0.4% following training (p < 0.001). The forearm blood flow ratio to ACh was significantly improved (analysis of variance, p < 0.05). Responses to SNP and GTN were unchanged. Endothelium-dependent vasodilation was enhanced in both conduit and resistance vessels. CONCLUSIONS: If endothelial dysfunction is an integral component of the pathogenesis of vascular disease, as currently believed, this study supports the value of an exercise program in the management of type 2 diabetes.
Diabetes Mellitus, Type 2↗
The level of accuracy and agreement in measures of FEO2, FECO2 and VE between the Cosmed K4b2 portable, respiratory gas analysis system and a metabolic cart.
This study aimed to assess the accuracy of the Cosmed K4b2 (Cosmed, Italy) portable metabolic system that measures FEO2, FECO2 and VE on a breath by breath basis. For gas concentration comparisons, expired air from 20 subjects performing treadmill running was collected in a 600 litre chain compensated Collins Tissot tank and analysed for FEO2 and FECO2 using a laboratory metabolic cart and the Cosmed K4 b2 metabolic system. For ventilation comparisons, serial steady state VE (STPD) values were measured on 10 subjects using the Cosmed K4b2 ventilation turbine and a Morgan ventilation monitor during a continuous treadmill running protocol at ascending speeds of 8, 11 and 14 km x h(-1). The Cosmed K4b2 FEO2 and FECO2 measures were significantly lower (P < 0.001) than the metabolic cart values. Pearson correlation coefficients (r) and the standard error of measurement (SEM) demonstrated a high association between the Cosmed and the metabolic cart measures (FEO2 r =0 .971, SEM 0.071: FECO2 r = 0.925, SEM 0.087). Cosmed VE (l x min(-1)) measures were significantly greater than Morgan values at running speeds of 8 kmh(-1) (P < 0.001) and 11 kmh(-1) (P < 0.001) but not significantly different at 14 km x h(-1) (P > 0.05). When VE measures at the three running speeds were combined, the mean difference between instrument measures ranged between 3.5 - 4.0 l x min(-1) but the values were highly correlated (r= 0.982, P<0.01; SEM 3.03). Linear regression analysis revealed the following regression equations to predict metabolic cart values from Cosmed measures: FEO2 = 0.852+0.963 Cosmed (R2 = 0.940, P<0.00 1), FECO2 = 0.627+0.878 Cosmed (R2=0.856, P<0.001), VE = -2.50+0.984 Cosmed (R2 = 0.965. P < 0.001). The results indicated that the Cosmed K4b2 unit assessed here produced measures of FEO2, FECO2 and VE that had strong correlation to values obtained from a metabolic cart. However, linear regression analysis may further improve the accuracy of Cosmed K4b2 measures when compared to metabolic cart values.
Adolescent↗
Weathering the storm: beta-blockade and the potential for disaster in severe hyperthyroidism.
Some patients with advanced thyrotoxicosis have occult cardiac dysfunction. The use of long-acting beta-blockers, traditional in the management of thyrotoxicosis, may have disastrous consequences in this setting. The following report documents the cardiovascular collapse and asystolic arrest of a patient with hyperthyroidism when treated with sotolol. Though the patient was successfully resuscitated, the long duration of action of sotolol necessitated prolonged inotropic and vasopressor support. A shorter acting beta-blocker, such as esmolol, theoretically may be a safer option.
Adrenergic beta-Antagonists↗
Recombinant human factor VIIa in the management of amyloid-associated factor X deficiency.
Factor X deficiency is an important complication of amyloidosis. It is associated with severe bleeding that is difficult to control with plasma or prothrombin complex concentrates. Splenectomy ameliorates the factor X deficiency, but achieving satisfactory haemostasis for this operation is problematic. We report that a new clotting concentrate, recombinant factor VIIa, readily controls bleeding and makes splenectomy feasible.
Amyloidosis↗
Acquired hemophilia.
Acquired hemophilia is a serious coagulopathy usually affecting the elderly, persons with autoimmune disorders and, infrequently, women in the immediate postpartum period. It is due to autoantibodies directed against specific domains of the factor VIII molecule, leading to inhibition of factor VIII binding to von Willebrand factor, to activated factor IX or to negatively charged phospholipids. This results in bleeding into the skin, muscles, gastrointestinal and genitourinary tracts, and other sites. Mixing patient plasma with normal plasma prolongs the activated partial thromboplastin time of the normal plasma and the Bethesda assay provides a quantitative estimate of the strength of the inhibitor. The selection of therapeutic concentrates for the management of acute bleeding is related to the titer of the inhibitor; if less than 5 Bethesda Units, human factor VIII may be effective, but higher titer inhibitors usually respond only to porcine factor VIII, recombinant factor VIIa or activated prothrombin complex concentrates. Corticosteroid treatment leads to disappearance of the autoantibody in 50% of patients; cyclophosphamide and cyclosporine are effective in many who do not respond to steroids. Occasionally, high dose intravenous immunoglobulin or immunosorbent columns transiently decrease inhibitor titers and enable control of bleeding. Other autoantibodies have been described against factors V, VII, XI and, rarely, factor XIII and prothrombin. New approaches in the management of autoimmune disease and, especially, methods to establish tolerance are in development.
Adrenal Cortex Hormones↗
Treatment of minocycline-induced cutaneous pigmentation with the Q-switched Alexandrite laser and a review of the literature.
Cutaneous pigmentation associated with minocycline ingestion is an unusual adverse effect for which few treatments have been described. Within the past few years, treatment with different Q-switched lasers has been reported in the literature. The purpose of this therapeutic intervention was to determine whether the Q-switched Alexandrite laser could clinically and histologically improve pigmentation associated with minocycline ingestion. A patient with type II minocycline pigmentation was treated with the Q-switched Alexandrite (755 nm) laser and then evaluated clinically and histologically to determine the outcome of this intervention. Treatment with the Q-switched Alexandrite (755 nm) laser provided excellent clinical and histologic clearing of minocycline pigmentation. One year after completion of laser treatment, the skin has remained clinically clear with no recurrence. The Q-switched Alexandrite laser (755 nm) should be considered for treatment of type II minocycline pigmentation.
Acne Vulgaris↗
Exercise training, vascular function, and functional capacity in middle-aged subjects.
PURPOSE: The aim of this study was to investigate the effect of 8 wk of exercise training on functional capacity, muscular strength, body composition, and vascular function in sedentary but healthy subjects by using a randomized, crossover protocol. METHODS: After familiarization sessions, 19 subjects aged 47 +/- 2 yr (mean +/- SE) undertook a randomized, crossover design study of the effect of 8 wk of supervised circuit training consisting of combined aerobic and resistance exercise. Peak oxygen uptake (.VO(2peak)), sum of 7 maximal voluntary contractions and the sum of 8 skinfolds and 5 segment girths were determined at entry, crossover, and 16 wk. Endothelium-dependent and -independent vascular function were determined by forearm strain-gauge plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP) in 16 subjects. RESULTS: Training did not alter ACh or SNP responses. .VO(2peak), (28.6 +/- 1.1 to 32.6 +/- 1.3 mL.kg(-1).min(-1), P < 0.001), exercise test duration (17.4 +/- 1.1 to 22.1 +/- 1.2 min, P < 0.001), and muscular strength (465 +/- 27 to 535 +/- 27 kg, P < 0.001) significantly increased after the exercise program, whereas skinfolds decreased (144 +/- 10 vs 134 +/- 9 mm, P < 0.001). CONCLUSION: These results suggest that moderate intensity circuit training designed to minimize the involvement of the arms improves functional capacity, body composition, and strength in healthy, middle-aged subjects without significantly influencing upper limb vascular function. This finding contrasts with previous studies in subjects with type 2 diabetes and heart failure that employed an identical training program.
Anthropometry↗