Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 93
Filter
1.
Ann Med ; 54(1): 1265-1276, 2022 12.
Article in English | MEDLINE | ID: mdl-35510813

ABSTRACT

BACKGROUND: Lower socioeconomic status (SES) is associated with higher mortality rates and the likelihood of receiving less evidence-based treatment after stroke. In contrast, little is known about the impact of SES on recovery after discharge from inpatient rehabilitation. The aim of this study was to investigate the influence of SES on long-term recovery after stroke. PATIENTS AND METHODS: In a prospective, observational, multicentre study, inpatients were recruited towards the end of rehabilitation. The 12-month follow-up focussed on upper limb motor recovery, measured by the Fugl-Meyer score. A clinically relevant improvement of ≥5.25 points was considered recovery. Patient-centric measures such as the Patient-reported Outcomes Measurement Information System-Physical Health (PROMIS-10 PH) provided secondary outcomes. Information on schooling, vocational training, income and occupational status pre-stroke entered a multidimensional SES index. Multivariate logistic regression models calculating odds ratios (ORs) and corresponding confidence intervals (CIs) were applied. SES was added to an initial model including age, sex and baseline neurological deficit. Additional exploratory analyses examined the association between SES and outpatient treatment. RESULTS: One hundred and seventy-six patients were enrolled of whom 98 had SES and long-term recovery data. Model comparisons showed the SES-model superior to the initial model (Akaike information criterion (AIC): 123 vs. 120, Pseudo R2: 0.09 vs. 0.13). The likelihood of motor recovery (OR = 17.12, 95%CI = 1.31; 224.18) and PROMIS-10 PH improvement (OR = 20.76, 95%CI = 1.28; 337.11) were significantly increased with higher SES, along with more frequent use of outpatient therapy (p = .02). CONCLUSIONS: Higher pre-stroke SES is associated with better long-term recovery after discharge from rehabilitation. Understanding these factors can improve outpatient long-term stroke care and lead to better recovery.KEY MESSAGEHigher pre-stroke socioeconomic status (SES) is associated with better long-term recovery after discharge from rehabilitation both in terms of motor function and self-reported health status.Higher SES is associated with significantly higher utilization of outpatient therapies.Discharge management of rehabilitation clinics should identify and address socioeconomic factors in order to detect individual needs and to improve outpatient recovery. Article registration: clinicaltrials.gov NCT04119479.


Subject(s)
Neurological Rehabilitation , Stroke Rehabilitation , Stroke , Humans , Inpatients , Prospective Studies , Recovery of Function , Social Class , Stroke Rehabilitation/methods , Treatment Outcome , Upper Extremity
2.
J Perinatol ; 41(7): 1725-1731, 2021 07.
Article in English | MEDLINE | ID: mdl-33649437

ABSTRACT

OBJECTIVE: To assess the feasibility of using an ordinary digital video camera to measure heart rate and detect oxygen desaturations in healthy infants. STUDY DESIGN: Heart rate and oxygen saturation were measured with a video camera by detecting small color changes in 28 infants' foreheads and compared with standard pulse oximetry measures. Multivariable regression examined the relationship between infant characteristics and heart-rate measurement precision. RESULTS: The average bias of camera heart-rate measures was -4.2 beats per minute (BPM) and 95% limits of agreement were ±43.8 BPM. Desaturations detected by camera were 75% sensitive (15/20) and had a positive predictive value of 20% (15/74). Lower birth-weight was independently correlated with more precise heart-rate measures (8.05 BPM per kg, [95% CI 0.764-15.3]). CONCLUSIONS: A digital video camera provides accurate but imprecise measures of infant heart rate and may provide a rough screening tool for oxygen desaturations.


Subject(s)
Oximetry , Photoplethysmography , Heart , Heart Rate , Humans , Infant , Oxygen
3.
Simul Healthc ; 13(2): 96-106, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29621100

ABSTRACT

INTRODUCTION: Simulation has become an integral tool in healthcare facility redesign. Immersing clinical experts into their future environment has demonstrated benefits for transition planning. This study evaluates translation of a proven macrosystems testing protocol, TESTPILOT, to an organization with limited simulation experience. METHODS: An experienced TESTPILOT team guided Woman's Hospital Baton Rouge's simulation preparation for their new neonatal intensive care unit. Metrics included participant evaluations, latent safety threats (LST), and clinician surveys. Latent safety threats recorded during debriefings were addressed by workflow committees. Clinicians were surveyed at four time points for readiness and preparedness on 24 key processes. RESULTS: The local team invested nearly 750 hours into learning and implementing seven simulations that participants rated positively. Most of the 305 LST were minor issues. Surveys at baseline (42% of staff), postsim (18%), pretransition (26%), and postmove (29%) demonstrated strong internal consistency. System readiness lagged behind staff preparedness (P < 0.007); both were higher after simulations (P ≤ 0.001) but at no other interval. Critical laboratory notification, rounding structure, team coverage, and feedback were still evolving as of move day (P < 0.02). DISCUSSION: Macrosystems testing using simulation identifies LST, improves process, and prepares staff. The methodology is implementable in organizations with limited prior exposure. Woman's Hospital Baton Rouge accrued essential skills to model and orchestrate an immersive neonatal intensive care unit and then drive effective multidisciplinary debriefings. Staff immersed in the new environment began to articulate their jobs before moving in. The trajectory of system readiness improvement corroborated LST correction. Future research is needed to determine the extent of simulation required for different organizational structures.


Subject(s)
Medical Staff, Hospital/education , Simulation Training/organization & administration , Female , Hospital Design and Construction , Humans , Intensive Care Units, Neonatal , Male , Patient Safety , Surveys and Questionnaires
4.
Aliment Pharmacol Ther ; 47(12): 1661-1672, 2018 06.
Article in English | MEDLINE | ID: mdl-29696671

ABSTRACT

BACKGROUND: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. AIM: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. METHODS: A single-arm, open-label, multicentre, intrapatient dose-escalation, phase 2 study with 4 phases: screening, 3-month SC (subcutaneous), 3-month IM (intramuscular) and 6-month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3-month SC phase. A ≥50% response rate was considered clinically relevant. RESULTS: Forty-three patients with late dumping were enrolled; 33 completed the 3-month SC phase and 23 completed the 12-month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%-75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0-12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). CONCLUSION: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.


Subject(s)
Dumping Syndrome/drug therapy , Quality of Life , Somatostatin/analogs & derivatives , Adult , Aged , Diarrhea/chemically induced , Female , Humans , Male , Middle Aged , Nausea/chemically induced , Somatostatin/therapeutic use
5.
Clin Rehabil ; 31(2): 250-261, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27072153

ABSTRACT

OBJECTIVE: To investigate the effectiveness of a multi-component evidence-based education programme on disease modifying therapies in multiple sclerosis. DESIGN: Controlled trial with two consecutive patient cohorts and a gap of two months between cohorts. SETTING: Three neurological rehabilitation centres. SUBJECTS: Patients with multiple sclerosis within rehabilitation. INTERVENTIONS: Control group (CG) participants were recruited and received standard information. Two months later, intervention group (IG) participants were recruited and received a six-hour nurse-led interactive group education programme consisting of two parts and a comprehensive information brochure. MAIN MEASURES: Primary endpoint was "informed choice", comprising of adequate risk knowledge in combination with congruency between attitude towards immunotherapy and actual immunotherapy uptake. Further outcomes comprised risk knowledge, decision autonomy, anxiety and depression, self-efficacy, and fatigue. RESULTS: A total of 156 patients were included (IG=75, CG=81). The intervention led to significantly more participants with informed choice (IG: 47% vs. CG: 23%, P=0.004). The rate of persons with adequate risk knowledge was significantly higher in the IG two weeks after the intervention (IG: 54% vs. CG: 31%, P=0.007), but not after six months (IG: 48% vs. CG: 31%, P=0.058). No significant differences were shown for positive attitude towards disease modifying therapy (IG: 62% vs. CG: 71%, P=0.29) and for disease modifying therapy status after six months (IG: 61.5% vs CG: 68.6%, P=0.39). Also no differences were found for autonomy preferences and decisional conflict after six months. CONCLUSION: Delivering evidence-based information on multiple sclerosis disease modifying therapies within a rehabilitation setting led to a marked increase of informed choices.


Subject(s)
Decision Making , Health Knowledge, Attitudes, Practice , Immunotherapy/methods , Multiple Sclerosis/therapy , Patient Education as Topic/organization & administration , Adult , Analysis of Variance , Chi-Square Distribution , Female , Humans , Male , Middle Aged , Multiple Sclerosis/diagnosis , Multiple Sclerosis/immunology , Observer Variation , Prognosis , Program Development , Program Evaluation , Prospective Studies , Risk Assessment , Severity of Illness Index , Single-Blind Method , Treatment Outcome
6.
Air Med J ; 35(3): 126-31, 2016.
Article in English | MEDLINE | ID: mdl-27255873

ABSTRACT

OBJECTIVE: Post-war Kosovar health care systems have reduced gaps in maternal and newborn health care. Coordinated neonatal transport programs may further improve survival and morbidities. METHODS: Transport care paradigms were tested using in situ (Kosovo) and ex situ (the United States) mobile immersive simulation. Patient demographics and outcomes were measured at the tertiary referral center. RESULTS: Four paired physician and nurse transport teams performed 7 simulated interfacility transports across Kosovo. In situ simulations revealed safety threats in facilities, ambulances, and team process. Ex situ observations reinforced roles and professionalism. For the first year after simulations, tertiary neonatal intensive care unit admissions were more premature (-2.4 weeks), smaller (-725 g), and out born (+12%). Mortality was higher (14.7% vs. 7.8%), hypothermia was lower (0.2% vs. 4.6%), and culture-positive sepsis was lower (15.7% vs. 42.9%). CONCLUSION: In situ augmented by ex situ simulation provided perspective and depth of understanding to implement a new care delivery paradigm. Simulations involving Kosovar health care providers across a network of facilities generated practical experience in nationwide neonatal transport, with temporal association to altered referral patterns at the tertiary care facility.


Subject(s)
Intensive Care, Neonatal/organization & administration , Transportation of Patients/organization & administration , Air Ambulances/organization & administration , Computer Simulation , Female , Humans , Infant, Newborn , Intensive Care, Neonatal/methods , Kosovo , Male , Transportation of Patients/methods
7.
J Perinat Med ; 44(4): 461-7, 2016 May 01.
Article in English | MEDLINE | ID: mdl-26115488

ABSTRACT

OBJECTIVES: We hypothesize that a formal simulation curriculum prepares neonatology fellows for difficult conversations better than traditional didactics. METHODS: Single-center neonatology fellowship graduates from 1999 to 2013 were sent a retrospective web-based survey. Some had been exposed to a Difficult Conversations curriculum (simulation group), others had not (no simulation group). The simulation group participated in one workshop annually, consisting of lecture, simulation, and debriefing. Scenarios were customized to year of training. Epoch comparisons were made between the simulation and no simulation groups. RESULTS: Self-rated baseline effectiveness at discussing difficult topics was not different. The simulation group reported more supervised family meetings and feedback after fellow-led meetings. Simulations were rated very positively. The simulation group reported increased comfort levels. Strategic pause and body positioning were specific communication skills more frequently acquired in the simulation group. In both groups, the highest ranked contributors to learning were mentor observation and clinical practice. In the simulation group, simulation and debriefing outranked didactics or other experiences. CONCLUSIONS: Simulation-based workshops improve communication skills in high stakes conversations. However, they do not substitute for mentor observation and experience. Establishing a structured simulation-based difficult conversations curriculum refines vital communication skills necessary for the high stakes conversations neonatologists direct in clinical practice.


Subject(s)
Communication , Neonatology , Professional-Patient Relations , Computer Simulation , Curriculum , Fellowships and Scholarships , Female , Humans , Infant, Newborn , Male , Models, Educational , Neonatology/education , Parents , Pregnancy , Terminal Care
8.
J Perinatol ; 33(2): 147-53, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22678140

ABSTRACT

OBJECTIVE: Hospital length of stay (LOS) is important to administrators and families of neonates admitted to the neonatal intensive care unit (NICU). A prediction model for NICU LOS was developed using predictors birth weight, gestational age and two severity of illness tools, the score for neonatal acute physiology, perinatal extension (SNAPPE) and the morbidity assessment index for newborns (MAIN). STUDY DESIGN: Consecutive admissions (n=293) to a New England regional level III NICU were retrospectively collected. Multiple predictive models were compared for complexity and goodness-of-fit, coefficient of determination (R (2)) and predictive error. The optimal model was validated prospectively with consecutive admissions (n=615). Observed and expected LOS was compared. RESULT: The MAIN models had best Akaike's information criterion, highest R (2) (0.786) and lowest predictive error. The best SNAPPE model underestimated LOS, with substantial variability, yet was fairly well calibrated by birthweight category. LOS was longer in the prospective cohort than the retrospective cohort, without differences in birth weight, gestational age, MAIN or SNAPPE. CONCLUSION: LOS prediction is improved by accounting for severity of illness in the first week of life, beyond factors known at birth. Prospective validation of both MAIN and SNAPPE models is warranted.


Subject(s)
Infant, Newborn, Diseases/diagnosis , Intensive Care Units, Neonatal/statistics & numerical data , Length of Stay/statistics & numerical data , Models, Statistical , Benchmarking , Birth Weight , Cohort Studies , Female , Gestational Age , Humans , Infant, Newborn , Infant, Newborn, Diseases/therapy , Male , Multivariate Analysis , New England , Predictive Value of Tests , Regression Analysis , Retrospective Studies , Risk Factors , Severity of Illness Index
9.
Obes Surg ; 22(10): 1521-6, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22588846

ABSTRACT

BACKGROUND: Diabetes surgery in nonobese or moderately obese patients is an emerging topic. The identification of preoperative factors predicting diabetes outcome following bariatric surgery, especially for metabolic nonresponders, is imperative. METHODS: Between 2005 and 2011, 235 patients underwent bariatric surgery for morbid obesity. Eighty-two of 235 patients had type 2 diabetes mellitus (T2DM). Data from this subgroup were investigated with univariate and multivariate analyses to identify predictors for metabolic nonresponse after surgery. RESULTS: Diabetes did not improve in 17/82 patients within 3 months after surgery. No correlation between excess body weight loss and metabolic response was detected. In univariate analysis, preoperative duration of diabetes was significantly longer in the nonresponder group (9.146 vs. 6.270 years; *p = 0.016), preoperative HbA1c levels were significantly higher among the nonresponders than among the responders (8.341 vs. 7.781 %; *p = 0.033), and more patients in the nonresponder group were reliant on a multi-drug approach preoperatively (*p = 0.045). In multivariate analysis, age, preoperative doses of insulin, and preoperative oral antidiabetics showed positive correlation to metabolic nonresponse after surgery (*p = 0.04; *p = 0.021; *p = 0.021). Metabolic failure rate was lower after Roux-en-Y gastric bypass compared to other bariatric procedures (**p = 0.008). CONCLUSIONS: A long history of preoperative T2DM, high preoperative HbA1c levels, and a preoperative therapy consisting of diverse approaches to diabetes treatment may be factors predicting failure of diabetes improvement in the early postoperative course after bariatric surgery. Age, preoperative insulin, and oral antidiabetic medication can be regarded as independent, significant predictors for metabolic outcome after bariatric surgery.


Subject(s)
Bariatric Surgery , Blood Glucose/metabolism , Body Mass Index , Diabetes Mellitus, Type 2/metabolism , Glycated Hemoglobin/metabolism , Obesity, Morbid/metabolism , Adult , Bariatric Surgery/methods , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/surgery , Female , Germany , Humans , Logistic Models , Male , Middle Aged , Obesity, Morbid/physiopathology , Obesity, Morbid/surgery , Patient Selection , Postoperative Period , Remission Induction , Risk Factors , Treatment Failure , Weight Loss
10.
Semin Perinatol ; 35(2): 80-3, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21440815

ABSTRACT

Macro-systems simulation is a methodology to assess existing services and support major culture shift to a new healthcare environment. Given credible local precedent, simulation can be effective for orienting staff, identifying process gaps and enabling their refinement prior to the transition. Select strategies enable staged process translation in an intensive care unit without exposing patients to potential risk. Orchestrating immersive, realistic in-situ simulations minimizes surprises at transition and enhances patient satisfaction. Such endeavors substantially elevate the perception of the value of simulation within an institution.


Subject(s)
Intensive Care Units, Neonatal , Patient Simulation , Female , Humans , Infant, Newborn , Pregnancy
11.
Acta Paediatr ; 99(5): 673-678, 2010 May.
Article in English | MEDLINE | ID: mdl-20105142

ABSTRACT

OBJECTIVES: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18-22 months corrected age in extremely low birth weight infants. METHOD: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 +/- 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18-22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. RESULTS: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. CONCLUSIONS: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18-22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.


Subject(s)
Bilirubin/blood , Developmental Disabilities/epidemiology , Health Status , Hyperbilirubinemia, Neonatal/complications , Infant Mortality , Infant, Extremely Low Birth Weight/growth & development , Cerebral Palsy/etiology , Developmental Disabilities/etiology , Follow-Up Studies , Hearing Loss/etiology , Humans , Hyperbilirubinemia, Neonatal/mortality , Infant, Extremely Low Birth Weight/blood , Infant, Newborn , Logistic Models , Risk Factors
12.
Horm Metab Res ; 41(12): 886-92, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19701877

ABSTRACT

The polyol isomalt (Palatinit) is a very low glycaemic sugar replacer. The effect of food supplemented with isomalt instead of higher glycaemic ingredients like sucrose and/or starch hydrolysates on metabolic control in patients with type 2 diabetes was examined in this open study. Thirty-three patients with type 2 diabetes received a diet with foods containing 30 g/d isomalt instead of higher-glycaemic carbohydrates for 12 weeks. Metformin and/or thiazolidindiones were the only concomitant oral antidiabetics allowed during the study. Otherwise, the participants maintained their usual diet during the test phase, but were instructed to refrain from additional sweetened foods. Before start, after 6 weeks and 12 weeks (completion of the study), blood samples were taken and analysed for clinical routine parameters, metabolic, and risk markers. Thirty-one patients completed the study. The test diet was well accepted and tolerated. After 12 weeks, significant reductions were observed for: glycosylated haemoglobin, fructosamine, fasting blood glucose, insulin, proinsulin, C-peptide, insulin resistance (HOMA-IR), and oxidised LDL (an atherosclerosis risk factor). In addition, significant lower nonesterified fatty acid concentrations were found in female participants. Routine blood measurements and blood lipids remained unchanged. The substitution of glycaemic ingredients by isomalt and the consequent on reduction of the glycaemic load within otherwise unchanged diet was accompanied by significant improvement in the metabolic control of diabetes. The present study is in agreement with findings of previous reported studies in human subjects demonstrating beneficial effects of low glycaemic diets on glucose metabolism in patients with diabetes mellitus type 2.


Subject(s)
Cariogenic Agents/therapeutic use , Diabetes Mellitus, Type 2/diet therapy , Diabetes Mellitus, Type 2/metabolism , Disaccharides/therapeutic use , Glycemic Index/physiology , Sugar Alcohols/therapeutic use , Adipokines/blood , Body Weight , Carbohydrate Metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/urine , Diet , Feces/chemistry , Female , Humans , Lipids/blood , Male , Middle Aged , Patient Compliance , Risk Factors , Time Factors
13.
Clin Biochem ; 40(3-4): 261-7, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17069786

ABSTRACT

OBJECTIVES: To assess the effects of sample dilution, peroxidase concentration, and chloride ion (Cl(-)) on plasma unbound bilirubin (B(f)) measurements made using a commercial peroxidase methodology (UB Analyzer) in a study population of ill, premature newborns. DESIGN AND METHODS: B(f) was measured with a UB Analyzer in 74 samples at the standard 42-fold sample dilution and compared with B(f) measured at a 2-fold sample dilution using a FloPro Analyzer. B(f) was measured at two peroxidase concentrations to determine whether the peroxidase steady state B(f) (B(fss)) measurements were significantly less than the equilibrium B(f) (B(feq)), in which case it was necessary to calculate B(feq) from the two B(fss) measurements. B(f) was also measured before and after adding 100 mmol/L Cl(-) to the UB Analyzer assay buffer. RESULTS: B(feq) at the 42-fold dilution was nearly 10-fold less than but it correlated significantly with B(feq) at the 2-fold dilution (mean 8.2+/-5.2 nmol/L versus 73.5+/-70 nmol/L, respectively, p<0.0001; correlation r=0.6). The two UB Analyzer B(fss) measurements were significantly less than B(feq) in 42 of 74 (57%) samples, and Cl(-) increased B(feq) in 66 of 74 (89%) samples by a mean of 82+/-67%. CONCLUSIONS: B(fss) measured by the UB Analyzer at the standard 42-fold sample dilution using assay buffer without Cl(-) and a single peroxidase concentration is significantly less than the B(feq) in undiluted plasma. Accurate B(f) measurements can be made only in minimally diluted serum or plasma.


Subject(s)
Analytic Sample Preparation Methods , Bilirubin/blood , Diagnostic Techniques and Procedures/instrumentation , Diagnostic Techniques and Procedures/standards , Infant, Premature/blood , Jaundice, Neonatal/diagnosis , Chlorides/chemistry , Female , Humans , Infant, Newborn , Peroxidases/chemistry
14.
Neuroscience ; 140(3): 897-911, 2006 Jul 07.
Article in English | MEDLINE | ID: mdl-16600521

ABSTRACT

Protein phosphatase 1 plays a major role in the governance of excitatory synaptic activity, and is subject to control via the neuromodulatory actions of dopamine. Mechanisms involved in regulating protein phosphatase 1 activity include interactions with the structurally related cytoskeletal elements spinophilin and neurabin, synaptic scaffolding proteins that are highly enriched in dendritic spines. The requirement for these proteins in dopamine-related neuromodulation was tested using knockout mice. Dopamine D1-mediated regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor activity was deficient in both striatal and prefrontal cortical neurons from neurabin knockout mice; in spinophilin knockout mice this deficit was manifest only in striatal neurons. At corticostriatal synapses long-term potentiation was deficient in neurabin knockout mice, but not in spinophilin knockout mice, and was rescued by a D1 receptor agonist. In contrast, long-term depression was deficient in spinophilin knockout mice but not in neurabin knockout mice, and was rescued by D2 receptor activation. Spontaneous excitatory post-synaptic current frequency was increased in neurabin knockout mice, but not in spinophilin knockout mice, and this effect was normalized by D2 receptor agonist application. Both knockout strains displayed increased induction of GluR1 Ser(845) phosphorylation in response to D1 receptor stimulation in slices, and also displayed enhanced locomotor activation in response to cocaine administration. These effects could be dissociated from cocaine reward, which was enhanced only in spinophilin knockout mice, and was accompanied by increased immediate early gene induction. These data establish a requirement for synaptic scaffolding in dopamine-mediated responses, and further indicate that spinophilin and neurabin play distinct roles in dopaminergic signal transduction and psychostimulant response.


Subject(s)
Brain/metabolism , Dopamine/metabolism , Microfilament Proteins/genetics , Nerve Tissue Proteins/genetics , Neuronal Plasticity/physiology , Phosphoprotein Phosphatases/metabolism , Animals , Corpus Striatum/metabolism , Dendritic Spines/drug effects , Dendritic Spines/metabolism , Dopamine Agonists/pharmacology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Long-Term Potentiation/genetics , Mice , Mice, Knockout , Motor Activity/drug effects , Motor Activity/genetics , Neural Pathways/metabolism , Organ Culture Techniques , Patch-Clamp Techniques , Prefrontal Cortex/metabolism , Protein Phosphatase 1 , Receptors, AMPA/metabolism , Receptors, Dopamine D1/agonists , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/agonists , Receptors, Dopamine D2/metabolism , Reward
15.
Prenat Diagn ; 25(7): 535-8, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16034828

ABSTRACT

Bruck syndrome is an autosomal recessive connective tissue disorder combining features of osteogenesis imperfecta and arthrogryposis multiplex congenita. There are only few reports describing this rare syndrome of multiple fractures and joint contractures that is thought to be a subtype of osteogenesis imperfecta. We report the first case of prenatal diagnosis of this syndrome in a fetus at 23 weeks of gestation. Ultrasound findings included brachycephaly, retrognathia marked shortening and bowing of both femurs, bilateral fixed flexion of the elbows, bilateral fixed extension of the wrists and partially fixed flexion of the knees. The parents opted for termination of pregnancy. Macroscopic and radiologic examination of the aborted fetus confirmed the prenatal diagnosis, whereas morphological studies of the bone tissue found no hard evidence of osteogenesis imperfecta, probably due to the early stage of pregnancy and the heterogeneity of the syndrome itself.


Subject(s)
Arthrogryposis/diagnosis , Osteogenesis Imperfecta/diagnosis , Prenatal Diagnosis , Abortion, Induced , Adult , Arthrogryposis/diagnostic imaging , Arthrogryposis/embryology , Diagnosis, Differential , Female , Humans , Osteogenesis Imperfecta/diagnostic imaging , Osteogenesis Imperfecta/embryology , Polyhydramnios , Pregnancy , Pregnancy Trimester, Second , Syndrome , Ultrasonography , Umbilical Arteries/abnormalities
16.
Genesis ; 31(3): 111-7, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11747201

ABSTRACT

The migrating cranial neural crest cells of birds, fish, and mammals have been shown to form the membranous bones of the cranium and face. These findings have been extrapolated to suggest that all the dermal bones of the vertebrate exoskeleton are derived from the neural crest ectomesenchyme. However, only one group of extant animals, the Chelonians, has an extensive bony exoskeleton in the trunk. We have previously shown that the autapomorphic carapacial and plastron bones of the turtle shell arise from dermal intramembranous ossification. Here, we show that the bones of the plastron stain positively for HNK-1 and PDGFRalpha and are therefore most likely of neural crest origin. This extends the hypothesis of the neural crest origin of the exoskeleton to include the turtle plastron.


Subject(s)
Bone and Bones/embryology , Neural Crest/embryology , Turtles/embryology , Animals , Bone and Bones/cytology , Bone and Bones/metabolism , Cell Lineage , Neural Crest/cytology , Neural Crest/metabolism , Osteogenesis , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Sulfotransferases/metabolism
17.
Fetal Diagn Ther ; 16(6): 427-32, 2001.
Article in English | MEDLINE | ID: mdl-11694751

ABSTRACT

We report a case of fetal cardiomegaly secondary to myocarditis as a result of intrauterine parvovirus B19 infection. The fetus was delivered through caesarean section because of increasing deterioration of cardiac function at 33 + 3 weeks with reverse flow in the ductus venosus. Four weeks later, a cardiac transplantation was carried out because of therapy-resistant dilative cardiomyopathy. This case shows that fetal parvovirus B19 infection may occur without anemia and myocarditis and does not always result in spontaneous reformation of a dilated heart and normal recovery. It may become the determining prognostic factor for the child.


Subject(s)
Cardiomyopathy, Dilated/etiology , Cardiomyopathy, Dilated/surgery , Fetal Diseases/virology , Heart Transplantation , Myocarditis/virology , Parvoviridae Infections/virology , Parvovirus B19, Human , Adult , Female , Gestational Age , Humans , Myocarditis/complications , Myocarditis/diagnostic imaging , Pregnancy , Ultrasonography, Prenatal
18.
Am J Gastroenterol ; 96(8): 2392-400, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11513180

ABSTRACT

OBJECTIVES: The aims of this study were to determine the frequency of different patterns of melanoma metastases to small bowel on radiological examination, and to assess the reliability of the most commonly used radiological methods for detecting these lesions. METHODS: The records of cases archived as melanoma metastatic to the small bowel of the Armed Forces Institute of Pathology were reviewed. The clinical information, type of imaging procedure performed, and radiological features were analyzed and compared to the findings at surgery and at autopsy. RESULTS: A total of 32 patients had clinical and surgical data with pathological confirmation. Seven patients had metastasis involving the duodenum, 22 had jejunal involvement, and 11 had ileal involvement. Metastases were categorized as polypoid, cavitary, infiltrating, or exoenteric. The polypoid pattern was seen in 20 patients (63%), six of whom showed multiple polypoid lesions (>10), referred to as polyposis. The "target lesion," a discrete polypoid mass with a central ulceration, was observed in only three (9%) of the 32 patients. Eight patients (25%) demonstrated a cavitary pattern, a circumferential mass with inner marginal necrosis, and five (16%) showed an infiltrating pattern. One patient (3%) had an exoenteric lesion with a fistulous tract. The small bowel follow-through demonstrated 32 of 55 metastases (sensitivity 58%). Contrast-enhanced CT demonstrated 32 of 48 masses (sensitivity 66%). Of the six cases of malignant polyposis, none were identified using CT, and only two were diagnosed by small bowel follow-through. CONCLUSIONS: The polypoid pattern, equally distributed between the jejunum and ileum, is the most common manifestation of metastatic melanoma to the small bowel. The target lesion was infrequently seen in this series. Small bowel follow-through and conventional CT seem to be unreliable in demonstrating melanoma metastases to the small bowel.


Subject(s)
Intestinal Neoplasms/diagnostic imaging , Intestinal Neoplasms/secondary , Intestine, Small , Melanoma/pathology , Skin Neoplasms/pathology , Adult , Female , Humans , Intestinal Neoplasms/surgery , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray Computed
19.
Nephrol Dial Transplant ; 16(8): 1592-7, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11477160

ABSTRACT

BACKGROUND: Acute deterioration of renal function is an important side-effect of angiotensin-converting enzyme (ACE) inhibitors, especially if accompanied by other nephrotoxic events. Angiotensin II receptor(1) blockers (ARB) are thought to have fewer side-effects on renal perfusion and function. We examined the effects of valsartan (VAL) on kidney function as well as the contribution of the nitric oxide (NO) system in a rat model of ischaemic acute renal failure (ARF). METHODS: ARF was induced by 40 min of clamping of both renal arteries in female Sprague-Dawley rats. Renal haemodynamic and tubular parameters were determined during post-ischaemic infusion of vehicle, VAL, VAL and the NO-synthase substrate L-arginine, and VAL together with inhibition of NO synthases (NOS) by L-NMMA. RESULTS: Clamping induced acute renal failure with marked decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) accompanied by a rise in renal vascular resistance (RVR) and fractional sodium excretion. Valsartan caused a slight but significant improvement of GFR and RPF without full recovery of renal function and caused a lowering of RVR and tubular sodium loss. L-arginine-co-administration had no additive beneficial effect. Valsartan-induced changes were not significantly depressed by unspecific inhibition of NOS. CONCLUSIONS: Inhibition of the angiotensin II-receptor(1) diminishes the deleterious effects of ischaemia and reperfusion on glomerular function and on the renal microcirculation. An involvement of the NO system could not be demonstrated.


Subject(s)
Hemodynamics/drug effects , Ischemia/physiopathology , Renal Circulation , Reperfusion Injury/physiopathology , Tetrazoles/pharmacology , Valine/pharmacology , Acute Disease , Angiotensin Receptor Antagonists , Animals , Female , Kidney Glomerulus/physiopathology , Microcirculation/drug effects , Rats , Rats, Sprague-Dawley , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Renal Circulation/drug effects , Valine/analogs & derivatives , Valsartan
20.
Curr Surg ; 58(2): 205-208, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11275247

ABSTRACT

Enteroclysis uses contrast fluid distention of the small bowel through a jejunal catheter with flouroscopic imaging to identify abnormalities. Computed tomograpic enteroclysis (CT-E) adds cross-sectional imaging to identify small bowel pathology to include masses, gastrointestinal bleeding of unknown origin, and partial obstruction. Computed tomography-enteroclysis is being used more frequently in the assessment of patients with possible small bowel pathology. This study examines the applicability of CT-E and its superiority over conventional enteroclysis.A retrospective chart review was used to examine all CT-E and enteroclysis studies performed at our institution during a 24-month period (August 1997 to August 1999). All patients that had received CT-E or enteroclysis were divided into 3 categories; group I: small bowel mass, group II: gastrointestinal bleeding, and group III: partial small bowel obstruction (pSBO). All patients included had received other radiological procedures based on the indication for examination to include esophagogastroduodenoscopy, colonoscopy, CT, abdominal x-rays, barium enema, and upper gastrointestinal with small bowel follow-through.Forty-nine studies were performed, with enteroclysis or CT-E, used in 46 patients. Median age was 62 years (M:F, 1:1). In group 1 (n = 10), no masses were noted, but all patients identified as having a mass on previous studies (n = 6) were determined not to have a mass by CT-E (n = 1) and enteroclysis (n = 5). In group II (n = 19), 1 small bowel source (jejujunal arteriovenous malformation) was identified through CT-E, and all other studies in both categories were negative/normal. In group III (n = 20), 5 pSBO were identified through CT-E that had not been previously described.Enteroclysis and CT-E are both effective at disproving the presence of small bowel masses discovered through less-specific radiological methods. In terms of gastrointestinal bleeding, CT-E is as effective as enteroclysis at identifying source of bleeding and may have an added role through its ability to better identify anatomic relationships. Computed tomography-enteroclysis was able to determine the presence of pSBO in 5 patients that previously had been undiagnosed. In conclusion, enteroclysis remains an effective radiological study for examination of the small bowel. Computed tomography-enteroclysis matches that effectiveness with the added benefit on high-resolution anatomic images that serve it well as an additional diagnostic tool for the General Surgeon in patients with difficult to diagnose small bowel pathology.

SELECTION OF CITATIONS
SEARCH DETAIL
...