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1.
Thromb Update ; 3: 100048, 2021 May.
Article in English | MEDLINE | ID: mdl-38620639

ABSTRACT

Background: Patients with severe SARS-CoV-2 infection have been shown to have abnormal coagulation parameters and are at increased risk of thromboembolism. The optimal thromboprophylaxis regimen that minimizes thrombosis without increased risk of serious bleeding is uncertain. Objectives: To describe the efficacy and safety of increased intensity (enhanced) thromboprophylaxis in patients with COVID-19 admitted to the medical intensive care unit (MICU). Methods: This is a retrospective cohort analysis of patients with a diagnosis of COVID-19 admitted to the MICU of an urban safety net hospital. With the exception of patients being supported with extracorporeal membrane oxygenation or on chronic anticoagulation who received therapeutic dosing of anticoagulation, thromboprophylaxis was given as either enoxaparin or unfractionated heparin in doses higher than those recommended for standard prophylaxis, but lower than those used for therapeutic anticoagulation. Main results: Of the 120 patients managed with an enhanced thromboprophylaxis protocol, 6 (5%) experienced thromboembolism as a result of their COVID-19 disease (1 pulmonary embolus, 4 deep vein thromboses, and 1 arterial embolism). Four patients experienced major bleeding while receiving therapeutic anticoagulation. Conclusions: In critically ill patients with COVID-19, increased intensity (enhanced) thromboprophylaxis appears to be effective at preventing clinically significant thromboembolic events without an increased risk of serious bleeding.

2.
Development ; 127(18): 3899-911, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10952888

ABSTRACT

We have identified and characterized a zebrafish recessive maternal effect mutant, ichabod, that results in severe anterior and dorsal defects during early development. The ichabod mutation is almost completely penetrant, but exhibits variable expressivity. All mutant embryos fail to form a normal embryonic shield; most fail to form a head and notochord and have excessive development of ventral tail fin tissue and blood. Abnormal dorsal patterning can first be observed at 3.5 hpf by the lack of nuclear accumulation of (beta)-catenin in the dorsal yolk syncytial layer, which also fails to express bozozok/dharma/nieuwkoid and znr2/ndr1/squint. At the onset of gastrulation, deficiencies in expression of dorsal markers and expansion of expression of markers of ventral tissues indicate a dramatic alteration of dorsoventral identity. Injection of (beta)-catenin RNA markedly dorsalized ichabod embryos and often completely rescued the phenotype, but no measurable dorsalization was obtained with RNAs encoding upstream Wnt pathway components. In contrast, dorsalization was obtained when RNAs encoding either Bozozok/Dharma/Nieuwkoid or Znr2/Ndr1/Squint were injected. Moreover, injection of (beta)-catenin RNA into ichabod embryos resulted in activation of expression of these two genes, which could also activate each other. RNA injection experiments strongly suggest that the component affected by the ichabod mutation acts on a step affecting (beta)-catenin nuclear localization that is independent of regulation of (beta)-catenin stability. This work demonstrates that a maternal gene controlling localization of (beta)-catenin in dorsal nuclei is necessary for dorsal yolk syncytial layer gene activity and formation of the organizer in the zebrafish.


Subject(s)
Cytoskeletal Proteins/metabolism , Organizers, Embryonic/metabolism , Signal Transduction , Trans-Activators , Zebrafish Proteins , Zebrafish/embryology , Active Transport, Cell Nucleus , Animals , Body Patterning/genetics , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Cell Nucleus/metabolism , Cytoskeletal Proteins/genetics , Embryo, Nonmammalian , Epistasis, Genetic , Female , Gene Expression Regulation, Developmental , Genes, Recessive , Glycogen Synthase Kinase 3 , Immunohistochemistry , In Situ Hybridization , Microinjections , Mutation/genetics , Penetrance , Proto-Oncogene Proteins/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Wnt Proteins , Zebrafish/genetics , beta Catenin
3.
Mech Dev ; 92(2): 145-53, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10727854

ABSTRACT

Drosophila Germ cell-less (Gcl) has previously been shown to be important in early events during the formation of pole cells, which are the germ cell precursors in the fly. We have isolated a 524 amino acid mouse gene with 32% identity and 49% similarity to Drosophila gcl, termed mgcl-1. Like Drosophila Gcl, mGcl-1 localizes to the nuclear envelope. Ectopic expression of mgcl-1 in Drosophila rescues the gcl-null phenotype, indicating that mGcl-1 is a functional homologue of Gcl. mgcl-1 maps to chromosome 6 at 47.3 cM, and is expressed at low levels at all embryonic stages examined from 8.5 to 18.5 d.p.c. as well as in many adult tissues. Different from Drosophila gcl, mgcl-1 is not highly expressed at the time the primordial germ cells appear in the mouse, but high mgcl-1 expression is found in selected mouse adult male germ cells. The differences in these expression patterns in light of conserved activity between the two genes is discussed.


Subject(s)
Drosophila Proteins , Drosophila/genetics , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Spermatogenesis/genetics , Transcription Factors , Amino Acid Sequence , Animals , Chromosome Mapping , Cloning, Molecular , Conserved Sequence , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Drosophila/embryology , Embryo, Nonmammalian , Female , Gene Expression Regulation, Developmental , Genetic Complementation Test , Germ Cells , Intercellular Signaling Peptides and Proteins , Male , Mice , Molecular Sequence Data , Octamer Transcription Factor-3 , Subcellular Fractions
4.
Dev Biol ; 215(2): 288-97, 1999 Nov 15.
Article in English | MEDLINE | ID: mdl-10545238

ABSTRACT

The germ cell precursors of Drosophila (pole cells) are specified by maternally supplied germ plasm localized to the posterior pole of the egg. One component of the germ plasm, germ cell-less (gcl) mRNA, encodes a novel protein which specifically localizes to the nuclear envelope of the pole cell nuclei. In addition to its maternal expression, gcl is zygotically expressed through embryonic development. In this report, we have characterized a null allele of germ cell-less to determine its absolute requirement during development. We have found that gcl activity is required only for the establishment of the germ cell lineage. Most embryos lacking maternal gcl activity fail to establish a germline. No other developmental defects were detected. Examination of germline development in these mutant embryos revealed that gcl activity is required for proper pole bud formation, pole cell formation, and pole cell survival. Using this null mutant we have also assayed the activity of forms of Gcl protein with altered subcellular distribution and found that localization to the nuclear envelope is crucial for promoting pole cell formation, but not necessary to initiate and form proper pole buds. These results indicate that gcl acts in at least two different ways during the establishment of the germ cell lineage.


Subject(s)
Drosophila Proteins , Drosophila/embryology , Germ Cells/physiology , Nuclear Envelope/chemistry , Nuclear Proteins/physiology , Animals , Female , Intercellular Signaling Peptides and Proteins , Nuclear Proteins/analysis , Phenotype , Transcription, Genetic
5.
Am J Respir Crit Care Med ; 160(1): 69-76, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10390382

ABSTRACT

Right heart catheterization (RHC) is commonly used in the diagnosis and management of acute lung injury (ALI). However, controversy exists regarding RHC. We examined RHC use during the first 3 d of ALI in an observational study of 135 patients defined by American-European Consensus Conference criteria. Study parameters examined for association with RHC included the Acute Physiology and Chronic Health Evaluation (APACHE) III score, lung injury score (LIS), and 20 additional epidemiologic, clinical, and laboratory parameters. RHC was performed in 70 patients (52%) within the first 3 d of ALI. RHC was positively associated (p < 0.05) with a diagnosis of sepsis, APACHE III score, blood urea nitrogen (BUN), creatinine, net fluid balance, and positive end-expiratory pressure. RHC was negatively associated (p < 0.05) with mean arterial pressure (Pa) and PaO2/FIO2. Logistic regression identified four predictors for RHC placement: sepsis, PaO2/FIO2, BUN, and Pa. Initial right atrial and pulmonary artery occlusion pressure measurements demonstrated a moderately strong correlation (r = 0.72). Use of RHC was associated with a change in one or more therapeutic interventions (intravascular fluids, vasopressors, diuretics) in 78% of patients. In summary, patients receiving RHC during the first 3 d of ALI were more severely ill than those who did not receive RHC, and RHC was associated with a change in therapy in most patients.


Subject(s)
Atrial Function, Right/physiology , Cardiac Catheterization , Hemodynamics/physiology , Pneumonia, Aspiration/physiopathology , Respiratory Distress Syndrome/physiopathology , Shock, Septic/physiopathology , APACHE , Adult , Aged , Critical Care , Female , Humans , Male , Middle Aged , Pneumonia, Aspiration/diagnosis , Pneumonia, Aspiration/therapy , Positive-Pressure Respiration , Prognosis , Pulmonary Edema/diagnosis , Pulmonary Edema/physiopathology , Pulmonary Edema/therapy , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , Risk Factors , Shock, Septic/diagnosis , Shock, Septic/therapy , Treatment Outcome
6.
Electromyogr Clin Neurophysiol ; 38(6): 371-6, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9783124

ABSTRACT

We have reviewed the clinical and electrophysiologic features of eleven mechanically ventilated patients with asthma who developed persistent weakness following treatment with neuromuscular blocking agents and corticosteroids. All patients had electrophysiologic findings consistent with a myopathic process and no evidence of a neuromuscular transmission disorder or generalized neuropathy. Electrophysiologic improvement paralleled clinical improvement. The severity of the initial electrophysiologic findings did not predict the subsequent rate of recovery. All patients showed substantial recovery (to functional independence) over the first month.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Anti-Asthmatic Agents/adverse effects , Muscle, Skeletal/physiopathology , Neuromuscular Blocking Agents/adverse effects , Paralysis/physiopathology , Status Asthmaticus/complications , Adult , Electromyography , Female , Humans , Male , Middle Aged , Paralysis/etiology , Status Asthmaticus/drug therapy , Status Asthmaticus/physiopathology
7.
Chest ; 113(4): 1048-54, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9554646

ABSTRACT

OBJECTIVE: To compare thermodilution right ventricular end-diastolic volume index (RVEDVI) and pulmonary artery occlusion pressure (Ppao) as predictors of the hemodynamic response to a fluid challenge. DESIGN: Prospective cohort study. SETTING: Medical ICU of a university-affiliated county hospital and medical-surgical ICU of a community hospital. PATIENTS: Twenty-five critically ill patients who had one or more clinical conditions that suggested the possibility of inadequate preload. INTERVENTIONS: Thirty-six fluid challenges. Fluid (saline or colloid) was administered rapidly until the Ppao rose by at least 3 mm Hg. When a patient underwent more than one fluid challenge, these were given on separate days and for different clinical indications. MEASUREMENTS AND RESULTS: Responders (n=20; > or = 10% increase in stroke volume [SV]) and nonresponders (n=16; <10% increase in SV) differed with respect to baseline Ppao (10.0+/-3.4 vs 14.2+/-3.6 mm Hg; p=0.001), but not with respect to baseline RVEDVI (105+/-31 vs 119+/-33 mL/m2; p=0.22). There was a moderate correlation between RVEDVI and fluid-induced change in SV (r=0.44); the relationship between Ppao and change in SV was stronger (r=0.58). A positive response to fluid was observed in 4 of 9 cases in which RVEDVI exceeded 138 mL/m2, a threshold value that has been suggested to reliably predict a poor response to fluid. CONCLUSION: RVEDVI was not a reliable predictor of the response to fluid. As a predictor of fluid responsiveness, Ppao was superior to RVEDVI. In an individual patient, adequacy of preload is best assessed by an empiric fluid challenge.


Subject(s)
Fluid Therapy , Hemodynamics/physiology , Ventricular Function, Right/physiology , Adult , Aged , Blood Pressure , Critical Illness , Humans , Middle Aged , Predictive Value of Tests , Prospective Studies , Pulmonary Artery/physiopathology , Stroke Volume/physiology , Thermodilution
8.
Intensive Care Med ; 23(11): 1125-31, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9434917

ABSTRACT

OBJECTIVE: To assess the reliability of the pulmonary artery occlusion pressure (Ppao) when respiratory excursions in intrathoracic pressure are prominent. DESIGN: We studied 24 critically ill patients who had 15 mm Hg or more of respiratory excursion in their Ppao tracing. Large respiratory excursions resulted from respiratory muscle activity that persisted despite sedation and mechanical ventilation in the assist-control mode. From the Ppao tracing, the end-expiratory and mid-point values were recorded; the latter was measured halfway between end-expiration and the nadir due to inspiratory triggering. The Ppao was then re-measured after administration of a non-depolarizing muscle relaxant. SETTING: Medical intensive care unit of a university-affiliated teaching hospital. MEASUREMENTS AND RESULTS: The difference between the pre-relaxation end-expiratory Ppao and the relaxed Ppao was larger than the difference between the pre-relaxation mid-point Ppao and the relaxed Ppao (11 +/- 5 vs 3 +/- 3 mm Hg, p < 0.01). In 21 of 24 (88%) cases, the relaxed Ppao was more closely approximated by the mid-point Ppao than by the end-expiratory Ppao. The difference between the end-expiratory Ppao and the relaxed Ppao increased as the amount of respiratory excursion increased (r = 0.51; p < 0.01). CONCLUSIONS: In mechanically ventilated patients whose respiratory muscles produce large excursions in the Ppao, the end-expiratory Ppao is often much higher than the Ppao measured after muscle relaxation. The pre-relaxation mid-point Ppao and the relaxed Ppao are usually similar, but this may not be true in individual patients. In this setting, the Ppao measured after muscle relaxation probably provides the most clinically reliable estimate of left heart filling pressure.


Subject(s)
Arterial Occlusive Diseases/physiopathology , Pulmonary Wedge Pressure , Respiration, Artificial , Adult , Arterial Occlusive Diseases/therapy , Critical Care , Humans , Muscle Relaxation , Positive-Pressure Respiration, Intrinsic , Pressure , Reproducibility of Results , Respiratory Physiological Phenomena
9.
Dev Dyn ; 207(3): 344-54, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8922533

ABSTRACT

Skeletal patterning and morphogenesis in the developing limb are thought to be regulated by instructive factors and cues from the zone of polarizing activity (ZPA), the apical ectodermal ridge (AER), and the dorsal ectoderm. However, the activities of the ZPA and AER dwindle early in embryogenesis and soon after ceases, when in fact the proximal skeletal elements are still rudimentary in structure and the more distal ones are yet to become recognizable. Thus, we asked whether the chondrocytes emerging within each mesenchymal condensation may themselves start expressing properties similar to those of ZPA and/or AER and, in so doing, may bring skeletal development to completion. Indeed, we found that the cartilaginous, but not precartilaginous, tissues in early chick limbs possess ZPA-like properties. They expressed an endogenous factor related to Sonic hedgehog (Shh), most likely Indian hedgehog (Ihh), and when fragments were grafted to the anterior margin of host stage 16-20 chick wing buds, they induced supernumerary skeletal elements (polarizing activity). The acquisition of polarizing activity by the cartilaginous structures followed clear proximo-to-distal and posterior-to-anterior routes. Thus, (1) stage 25 cartilaginous humerus had polarizing activity while stage 25 prospective radius did not, (2) posteriorly-located stage 29 ulna had stronger activity than anteriorly-located stage 29 radius, and (3) ulna's diaphysis had stronger activity at stage 29 than 31 while radius's diaphysis was stronger at stage 31 than 29. Prior to inducing extra digit formation, the cartilaginous grafts induced Hoxd-12 and Hoxd-13 gene expression in adjacent competent mesenchymal tissue. Strikingly, the cartilaginous grafts activity also expression of Shh and polarizing activity in adjacent mesenchyme, which ZPA grafts cannot do; thus, the cartilaginous structures displayed activities "upstream" of those of the ZPA. The results support our hypothesis that chondrocytes may themselves direct skeletal morphogenesis. In so doing and as a result of their inductive activities, the cells may also have an important role in the completion of limb patterning and morphogenesis.


Subject(s)
Cartilage/metabolism , Extremities/embryology , Gene Expression , Proteins/genetics , Trans-Activators , Animals , Cartilage/embryology , Chick Embryo , Hedgehog Proteins , Homeodomain Proteins/genetics , Morphogenesis , Transcription Factors/genetics
10.
Exp Cell Res ; 229(1): 126-36, 1996 Nov 25.
Article in English | MEDLINE | ID: mdl-8940256

ABSTRACT

During endochondral ossification, chondrocytes progress through several stages of maturation before they are replaced by bone cells. Chondrocyte proliferation, the first step in this complex multistage process, is strictly controlled both spatially and temporally but its underlying mechanisms of regulation remain unclear. In this study we asked whether chondrocytes produce syndecan-3, a cell surface receptor for growth factors such as fibroblast growth factor 2 (FGF-2), and whether syndecan-3 may play a role in proliferation during chondrocyte maturation. We found that proliferating immature cartilage from chick embryo tibia and sternum contained significant amounts of syndecan-3 mRNA, whereas mature hypertrophic cartilage contained markedly lower transcript levels. Immunohistochemical analyses on sections of Day 18 chick embryo tibia revealed that syndecan-3 was spatially restricted and indeed detectable only in immature proliferating chondrocytes in the top zone of growth plate. These syndecan-3-rich proliferating chondrocytes lay beneath developing articular chondrocytes rich in their typical matrix protein tenascin-C, resulting in a striking boundary between these two populations of chondrocytes. Immature proliferating chondrocyte populations reared in growth-promoting culture conditions displayed strong continuous syndecan-3 gene expression; upon induction of maturation by vitamin C treatment, syndecan-3 gene expression was markedly down-regulated. Treatment with FGF-2 for 24 h stimulated both syndecan-3 gene expression and chondrocyte proliferation; this growth stimulation was counteracted by cotreatment with heparinase I or III. The results of the study indicate that syndecan-3 participates in the maturation of chondrocytes during endochondral ossification and represents a regulator of the proliferative phase of this multistage process.


Subject(s)
Cartilage, Articular/cytology , Cartilage, Articular/physiology , Fibroblast Growth Factor 2/pharmacology , Glucuronidase , Membrane Glycoproteins/physiology , Osteogenesis , Proteoglycans/physiology , Animals , Cartilage, Articular/embryology , Cell Division/drug effects , Cells, Cultured , Chick Embryo , Gene Expression Regulation, Developmental , Glycoside Hydrolases/pharmacology , Humans , Kinetics , Membrane Glycoproteins/biosynthesis , Membrane Glycoproteins/drug effects , Organ Specificity , Proteoglycans/biosynthesis , Proteoglycans/drug effects , Receptors, Fibroblast Growth Factor/physiology , Recombinant Proteins/pharmacology , Syndecan-3
11.
Clin Chest Med ; 17(3): 577-90, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8875012

ABSTRACT

This article reviews selected topics relevant to the use of mechanical ventilation in patients with severe airflow obstruction. Areas discussed include the bedside assessment of respiratory system mechanics, the ventilatory determinants of dynamic pulmonary hyperinflation, the role of controlled hypoventilation with permissive hypercapnia, and the delivery of bronchodilators during mechanical ventilation.


Subject(s)
Lung Diseases, Obstructive/therapy , Respiration, Artificial , Adrenal Cortex Hormones/therapeutic use , Airway Resistance , Bronchodilator Agents/therapeutic use , Humans , Hypercapnia/therapy , Lung Volume Measurements , Positive-Pressure Respiration , Respiration, Artificial/adverse effects , Respiratory Mechanics
13.
J Orthop Res ; 14(3): 403-12, 1996 May.
Article in English | MEDLINE | ID: mdl-8676253

ABSTRACT

The development of cartilaginous elements of long bone during embryogenesis and postnatal bone repair processes is a complex process that involves skeletal cells and surrounding mesenchymal periosteal cells. Relatively little is known of the mechanisms underlying these processes. Previous studies from this and other laboratories have suggested that the extracellular matrix protein tenascin-C is involved in skeletogenesis. Using in situ hybridization and immunofluorescence, we extended those studies by comparing the expression of tenascin-C with that of syndecan-3, which belongs to a family of cell surface receptors with which tenascins are known to interact. We found that syndecan-3 transcripts at first were very abundant in the presumptive periosteum surrounding the diaphysis of early chondrocytic skeletal elements in chick limb. As the elements developed further, syndecan-3 gene expression decreased in the diaphyseal periosteum, whereas it became stronger around the early epiphysis and within the forming articular cells. However, as the diaphyseal periosteum initiated osteogenesis and gave rise to the intramembranous bone collar, syndecan-3 gene expression increased again. At early stages of skeletogenesis: the tenascin-C gene exhibited patterns of expression that were similar to and temporally followed, those of the syndecan-3 gene. At later stages, however, tenascin-C gene expression was markedly reduced during intramembranous osteogenesis around the diaphysis. In addition, although syndecan-3 gene expression was low in osteoblasts and osteocytes located deep into trabecular bone, tenascin-C gene expression remained strong. Thus, tenascin-C and syndecan-3 display distinct temporal and spatial patterns of expression in periosteum and during the development of long bone. Given their multidomain structure and specific patterns of expression, these macromolecules may regulate site-specific skeletal processes, including interactions between developing periosteum and chondrocytes and delineation of the early cartilaginous skeletal elements.


Subject(s)
Membrane Glycoproteins/genetics , Periosteum/embryology , Proteoglycans/genetics , Receptors, Fibroblast Growth Factor/genetics , Tenascin/genetics , Animals , Bone Development/genetics , Chick Embryo , Fluorescent Antibody Technique , Gene Expression Regulation, Developmental/physiology , In Situ Hybridization , Periosteum/physiology , RNA, Messenger/analysis , Syndecan-3
14.
Am J Respir Crit Care Med ; 153(5): 1686-90, 1996 May.
Article in English | MEDLINE | ID: mdl-8630621

ABSTRACT

Patients who undergo mechanical ventilation for severe asthma are at risk of developing diffuse muscle weakness because of acute myopathy. The relative importance of corticosteroids and neuromuscular paralysis in causing the myopathy is controversial, and it is uncertain whether the chemical structure of the drug used to induce paralysis influences the risk of myopathy. Using a retrospective cohort study design, we evaluated 107 consecutive episodes of mechanical ventilation for severe asthma to assess (1) the incidence of clinically significant weakness in patients treated with corticosteroids alone versus corticosteroids with neuromuscular paralysis, (2) the influence of the duration of paralysis on the incidence of muscle weakness, and (3) the relative risk of weakness in patients paralyzed with the nonsteroidal drug atracurium versus an aminosteroid paralytic agent (pancuronium, vecuronium). The use of corticosteroids and a neuromuscular blocking agent was associated with a much higher incidence of muscle weakness as compared with the use of corticosteroids alone (20 of 69 versus O of 38, p < 0.001). The 20 weak patients were paralyzed significantly longer than the 49 patients who received a neuromuscular blocking agent without subsequent weakness (3.4 +/- 2.4 versus 0.6 +/- 0.7 d, p < 0.001). Eighteen of the 20 weak patients had been paralyzed for more than 24 h. The incidence of weakness was not reduced when paralysis was achieved with atracurium as opposed to an aminosteroid neuromuscular blocking agent. In conclusion, corticosteroid-treated patients with severe asthma who undergo prolonged neuromuscular paralysis are at significant risk for the development of muscle weakness, and the risk of weakness is not reduced by use of atracurium.


Subject(s)
Asthma/therapy , Muscle Weakness/etiology , Respiration, Artificial , Acute Disease , Adolescent , Adult , Aged , Albuterol/administration & dosage , Albuterol/therapeutic use , Atracurium/administration & dosage , Atracurium/adverse effects , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/therapeutic use , Cohort Studies , Female , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Humans , Incidence , Male , Methylprednisolone/adverse effects , Methylprednisolone/therapeutic use , Middle Aged , Muscular Diseases/etiology , Neuromuscular Nondepolarizing Agents/administration & dosage , Neuromuscular Nondepolarizing Agents/adverse effects , Pancuronium/administration & dosage , Pancuronium/adverse effects , Respiration, Artificial/adverse effects , Retrospective Studies , Risk Factors , Time Factors , Vecuronium Bromide/administration & dosage , Vecuronium Bromide/adverse effects
15.
Dev Dyn ; 206(1): 59-72, 1996 May.
Article in English | MEDLINE | ID: mdl-9019247

ABSTRACT

Tooth development involves reciprocal epithelial-mesenchymal interactions, polarized growth, mesenchyme condensation, and complex morphogenetic events. Because these processes bear similarities to those occurring in the developing limb, we asked whether morphogenetic signals found in the limb also occur in the developing tooth. We grafted mouse embryo tooth germs to the anterior margin of host chick embryo wing buds and determined whether the dental tissues had polarizing activity. Indeed, the grafts induced supernumerary digits. Activity of both molar and incisor tooth germs increased from bud to cap stages and was maximal at late bell stage in newborn. With further development the polarizing activity began to decrease, became undetectable in adult molar mesenchyme but persisted in incisor mesenchyme, correlating with the fact that incisors grow throughout postnatal life while molars do not. When different portions of neonatal incisors were assayed, a clear proximo-distal gradient of activity was apparent, with maximal activity restricted to the most proximal portion where undifferentiated mesenchyme and enamel organ reside. In situ hybridizations demonstrated that prior to induction of supernumerary digits, the tooth germ grafts induced expression in host tissue of Hoxd-12 and Hoxd-13. In addition, whole-mount in situ hybridizations and immunohistochemistry showed that developing tooth germs express Sonic hedgehog (Shh). Shh expression was first detected in bud stage tooth germs; at later stages Shh transcripts were prominent in enamel knot and differentiating ameloblasts at the cuspal region. We concluded that tooth germs possess polarizing activity and produce polarizing factors such as Shh. As in the limb, these factor(s) and activity probably play key roles in establishing polarity and regulating morphogenesis during early tooth development. Given its subsequent association with differentiating ameloblasts, Shh probably participates also in cytogenetic events during odontogenesis.


Subject(s)
Animals, Newborn/growth & development , Animals, Newborn/metabolism , Body Patterning , Proteins/metabolism , Tooth/embryology , Tooth/growth & development , Trans-Activators , Aging/metabolism , Animals , Chick Embryo , Embryonic and Fetal Development , Enamel Organ/embryology , Enamel Organ/growth & development , Hedgehog Proteins , Incisor/embryology , Incisor/growth & development , Mice/embryology , Mice/growth & development , Mice, Inbred Strains , Molar/embryology , Molar/growth & development , Tooth Germ/physiology , Tooth Germ/transplantation , Wings, Animal/abnormalities , Wings, Animal/embryology
16.
Crit Care Med ; 24(3): 541-6, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8625647

ABSTRACT

OBJECTIVE: To describe the occurrence of low measured auto-end-expiratory pressure (auto-PEEP) during mechanical ventilation of patients severe asthma. DESIGN: Observational clinical study. SETTING: Medical intensive care unit of a university-affiliated county hospital. PATIENTS: Four mechanically ventilated patients with severe asthma who had low measured auto-PEEP despite marked increase in both peak and plateau airway pressures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Peak pressure, plateau pressure, and auto-PEEP were measured at an early time point, when airflow obstruction was most severe, and again at a later time after clinical improvement. Auto-PEEP was measured by the method of end-expiratory airway occlusion. From the early to the late point, there was a marked decrease in peak pressure (76 +/- 7 to 53 +/- 6 cm H2O; p<.001) and in plateau pressure (28 +/- 2 to 18 +/- 3 cm H2O; p<.001), but only minimal change in auto-PEEP (5 +/- 3 to 4 +/- 3 cm H2O). The difference between plateau pressure and auto-PEEP decreased between the early and late time points (23 +/- 1 to 14 +/- 1 cm H2O; p<.01), even though tidal volume was larger at the late time point. In three patients, low auto-PEEP and a large difference between plateau pressure and auto-PEEP was only seen after expiratory time was prolonged. In these three patients, prolongation of expiratory time resulted in a large decrease in measured auto-PEEP (14 +/- 4 to 5 +/- 4 cm H2O), but a much smaller change in plateau pressure (31 +/- 3 to 29 +/- 3 cm H2O). CONCLUSIONS: We conclude that measured auto-PEEP may underestimate end-expiratory alveolar pressure in severe asthma, and that marked pulmonary hyperinflation may be present despite low measured auto-PEEP, especially at low respiratory rates. This phenomenon may be due to widespread airway closure that prevents accurate assessment of alveolar pressure at end-expiration.


Subject(s)
Asthma/complications , Positive-Pressure Respiration, Intrinsic/etiology , Respiration, Artificial , Acute Disease , Adult , Asthma/physiopathology , Asthma/therapy , Humans , Positive-Pressure Respiration, Intrinsic/diagnosis , Positive-Pressure Respiration, Intrinsic/physiopathology , Prospective Studies , Respiratory Mechanics , Time Factors
17.
Am J Public Health ; 85(12): 1684-9, 1995 Dec.
Article in English | MEDLINE | ID: mdl-7503345

ABSTRACT

OBJECTIVE: This study examined whether victimization prevention instruction in school has any impact on children's behavior in situations of real victimization threat. METHODS: Telephone interviews were conducted in 1992 with a nationally representative sample of youths aged 10 to 16 and their caretakers, and the experience of 1457 of these children was followed up more than a year later. RESULTS: Exposure to a more comprehensive prevention program was not associated with reduced incidence of victimization, injury, or upset. However, some of the exposure conditions were associated with an increased likelihood that the children would disclose victimizations, an increased likelihood that they would see themselves as having successfully protected themselves, and a decreased likelihood that they would blame themselves for the episode. Exposed children acquired some knowledge about sexual abuse and, when actually confronted by a threat, an ability to do the things they had been taught. A nonsignificant trend was also noted toward increased injury for exposed children during sexual assaults. CONCLUSION: These mixed findings suggest that prevention educators need to plan programs based on realistic goals for what can be accomplished.


Subject(s)
Child Abuse/prevention & control , Health Education/organization & administration , Preventive Health Services/organization & administration , School Health Services/organization & administration , Adolescent , Child , Child Abuse/psychology , Child Abuse/statistics & numerical data , Child Behavior , Female , Follow-Up Studies , Health Knowledge, Attitudes, Practice , Humans , Incidence , Male , Program Evaluation , Surveys and Questionnaires , United States/epidemiology
18.
Dev Dyn ; 203(2): 152-62, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7544653

ABSTRACT

The mechanisms by which the early limb cell condensations and interzone mesenchyme give rise to skeletal elements and joints are poorly understood. Previous work from this laboratory has shown that the extracellular matrix protein tenascin-C is associated with articular cartilage and joint tissue development; others have shown that tenascin-C may exert its biological activities via interactions with cell surface receptors, such as syndecans. To further analyze the roles of tenascin-C and its putative receptors in skeletal development, we carried out a detailed in situ hybridization analysis of tenascin-C and syndecan-3 gene expression during development of chick limb skeletal elements and joints. We found that as the early mesenchymal condensations chondrify around day 5 (E5) of development, they become surrounded by a thick syndecan-3 rich perichondrium while tenascin-C transcripts are much fewer and restricted to diaphyseal perichondrium and developing interzones. Similar patterns were observed as distal carpal and digit condensations formed in older embryos. As the cartilaginous long bone models elongated proximo-distally and joint formation proceeded with age, we observed that syndecan-3 transcripts decrease significantly along the diaphysis and remain very abundant along the metaphysis and in the epiphyseal articular cap and interzone. Conversely, tenascin-C RNAs remain abundant along the diaphysis and begin to increase at the epiphysis and in interzone-derived tissues, such as menisci and joint capsule. By E10, the skeletal elements have well-defined morphologies, endochondral ossification has initiated in their diaphysis, and diaphyseal perichondrium has become periosteum. These developmental changes were accompanied by equally marked changes in gene expression; these included a marked increase in tenascin-C gene expression in articular cap, fragmentation of tenascin-C gene expression along the periosteum, reinitiation of syndecan-3 gene expression in periosteum, and differential gene expression in osteoprogenitor cells. The sheer complexity of the gene expression patterns documented in this study attests to the complexity of processes that bring about normal skelatogenesis. Clearly, tenascin-C and syndecan-3 appear to be closely associated with several of these processes, particularly in establishing tissue boundaries (perichondrium and periosteum) between condensations and surrounding mesenchymal cells, in regulating perichondral cell differentiation and incorporation into the growing skeletal elements, and in the genesis of epiphyseal chondrocytes and associated joint tissues.


Subject(s)
Bone and Bones/embryology , Cartilage, Articular/embryology , Cartilage/embryology , Cell Adhesion Molecules, Neuronal/physiology , Extracellular Matrix Proteins/physiology , Membrane Glycoproteins/physiology , Proteoglycans/physiology , Animals , Cell Adhesion Molecules, Neuronal/genetics , Chick Embryo , Connective Tissue/embryology , Embryonic and Fetal Development , Extracellular Matrix Proteins/genetics , Gene Expression , Joints/embryology , Membrane Glycoproteins/genetics , Periosteum/embryology , Proteoglycans/genetics , Syndecan-3 , Tenascin
19.
Child Abuse Negl ; 19(2): 129-39, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7780776

ABSTRACT

The National Youth Victimization Prevention Study interviewed a representative sample of 2,000 U.S. children and their caretakers about the children's experience with child abuse and victimization prevention programs. Two-thirds of the children reported being exposed to at least one program at some time, 37% within the last year. Programs that gave children a chance to practice, that prompted discussions with parents, and that included information on dealing with bullies were more likely to result in utilization of the program skills. Although satisfaction levels were generally high for all groups, girls, black children, and children from lower socioeconomic status families, as well as their parents, had more positive reactions and reported more skill utilization. Some children did report, and their parents confirmed, more worry about abuse and fear of adults. However, the children with increased worry and fear were also the children who themselves and their parents reported the most positive feelings about the programs and the most skill utilization. This suggests that the level of worry and fear induced by the programs was appropriate to the subject.


Subject(s)
Child Abuse, Sexual/prevention & control , Child Abuse/prevention & control , Health Education , Adolescent , Adult , Anxiety/psychology , Child , Child Abuse/psychology , Child Abuse, Sexual/psychology , Consumer Behavior , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Parents/psychology , Program Evaluation , United States
20.
Child Abuse Negl ; 19(2): 141-53, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7780777

ABSTRACT

This study examined whether instruction in school and at home about how to prevent victimization has any impact on children's behavior in situations of real victimization threat. Telephone interviews were conducted in 1992 with a nationally representative sample of 2,000 youths age 10 to 16 and their caretakers. More comprehensive school programs had mixed, small but overall positive effects. Children exposed to such school-based prevention programs performed better on a short test of knowledge about sexual victimization; when victimized or threatened were more likely to use the self-protection strategies recommended by prevention educators; were more likely to feel that they had been successful in protecting themselves; and were more likely to disclose to someone about the victimization attempts. They were not better able to limit the seriousness of the assaults and, in fact, they experienced more injuries in the course of sexual assaults. Comprehensive parental instruction also had positive effects on knowledge, the use of preferred self-protection strategies and the likelihood of disclosure. Children with comprehensive parental instruction were more likely to limit the seriousness of assaults.


Subject(s)
Child Abuse, Sexual/prevention & control , Child Abuse/prevention & control , Health Education , Adolescent , Adult , Child , Child Abuse/psychology , Child Abuse, Sexual/psychology , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Parents/psychology , Program Evaluation , Self Disclosure , Treatment Outcome , United States , Wounds and Injuries/prevention & control , Wounds and Injuries/psychology
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