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1.
Sci Total Environ ; 742: 140524, 2020 Nov 10.
Article in English | MEDLINE | ID: mdl-32619842

ABSTRACT

Improving the food supply chain efficiency has been identified as an essential means to enhance food security, while reducing pressure on natural resources. Adequate food loss and waste (FLW) management has been proposed as an approach to meet these objectives. The main hypothesis of this study is to consider that the "strong fluctuations and short-term changes" on eating habits may have major consequences on potential FLW generation and management, as well as on GHG emissions, all taking into account the nutritional and the economic cost. Due to the exceptional lockdown measures imposed by the Spanish government, as a consequence of the emerging coronavirus disease, COVID-19, food production and consumption systems have undergone significant changes, which must be properly studied in order to propose strategies from the lessons learned. Taking Spain as a case study, the methodological approach included a deep analysis of the inputs and outputs of the Spanish food basket, the supply chain by means of a Material Flow Analysis, as well as an economic and comprehensive nutritional assessment, all under a life cycle thinking approach. The results reveal that during the first weeks of the COVID-19 lockdown, there was no significant adjustment in overall FLW generation, but a partial reallocation from extra-domestic consumption to households occurred (12% increase in household FLW). Moreover, the economic impact (+11%), GHG emissions (+10%), and the nutritional content (-8%) complete the multivariable impact profile that the COVID-19 outbreak had on FLW generation and management. Accordingly, this study once again highlights that measures aimed at reducing FLW, particularly in the household sector, are critical to make better use of food surpluses and FLW prevention and control, allowing us to confront future unforeseen scenarios.


Subject(s)
Coronavirus Infections , Pandemics , Pneumonia, Viral , Refuse Disposal , Waste Management , Betacoronavirus , COVID-19 , Disease Outbreaks , Food , Humans , SARS-CoV-2 , Spain
2.
Eur J Trauma Emerg Surg ; 43(4): 451-459, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28624992

ABSTRACT

PURPOSE: The main purpose of this systematic review was to investigate the effect of compression treatment on the perioperative course of ankle fractures and describe its effect on edema, pain, ankle joint mobility, wound healing complication, length of stay (LOS) and time to surgery (TTS). The aim was to suggest a recommendation to clinicians considering implementing compression therapy in the standard care of the ankle fracture patient, based on the existing literature. METHODS: We conducted a systematic search of literature including studies concerning adult patients with unstable ankle fractures undergoing surgery, testing either intermittent pneumatic compression, compression bandage and/or compression stocking and reporting its effect on edema, pain, ankle joint mobility, wound healing complication, LOS and TTS. To conclude on data a narrative synthesis was performed. RESULTS: The review included eight studies (451 patients). Seven studies found a significant effect on edema, two studies described a significant reduction in pain, one a positive effect on ankle movement, two a positive effect on wound healing, one a reduction in LOS and finally two studies reported reduction in TTS. A systematic bias assessment showed that the included studies had methodological limitations influencing the confidence in the effect estimate. CONCLUSIONS: Compression therapy has a beneficial effect on edema reduction and probably a positive effect on pain and ankle joint mobility, but with the methodological limitations in the included studies it is not possible to make a solid conclusion on the effect on wound healing, LOS and TTS.


Subject(s)
Ankle Fractures/surgery , Compression Bandages , Edema/prevention & control , Intermittent Pneumatic Compression Devices , Postoperative Complications/prevention & control , Humans , Length of Stay , Pain Measurement , Wound Healing
3.
Brain Struct Funct ; 222(6): 2507-2525, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28185007

ABSTRACT

Neurons producing melanin-concentrating hormone (MCH) are located in the tuberal lateral hypothalamus (LHA) and in the rostromedial part of the zona incerta (ZI). This distribution suggests that rostromedial ZI shares some common features with the LHA. However, its functions with regard to arousal or feeding, which are often associated with the LHA, have not been thoroughly investigated. This study analyses the responses in the tuberal LHA and adjacent rostromedial ZI after experiments related to arousal, exploration, food teasing and ingestive behavior. Specific aspects of the connections of the rostromedial ZI were also studied using retrograde and anterograde tract-tracing approaches. The rostromedial ZI is activated during exploratory and teasing experiments. It receives specific projections from the frontal eye field and the anterior pole of the superior colliculus that are involved in gaze fixation and saccadic eye movements. It also receives projections from the laterodorsal tegmental nucleus involved in attention/arousal. By contrast, the tuberal LHA is activated during wakefulness and exploratory behavior and reportedly receives projections from the medial prefrontal and insular cortex, and from several brainstem structures such as the periaqueductal gray. We conclude that the rostromedial ZI is involved in attentional processes while the adjacent tuberal LHA is involved in arousal.


Subject(s)
Arousal , Attention , Behavior, Animal , Hypothalamic Area, Lateral/metabolism , Neurons/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Zona Incerta/metabolism , Animals , Eating , Exploratory Behavior , Feeding Behavior , Hypothalamic Area, Lateral/cytology , Male , Neural Pathways/metabolism , Rats, Sprague-Dawley , Saccades , Zona Incerta/cytology
5.
J Clin Pathol ; 62(1): 89-91, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19103866

ABSTRACT

An unusual case of Epstein-Barr virus-negative primary extranodal B-cell non-Hodgkin's lymphoma involving six anatomical sites is described in a report that challenges the role of organotropism in the pathogenesis of extranodal lymphoma.


Subject(s)
Lymphoma, Large B-Cell, Diffuse/pathology , Diagnosis, Differential , Herpesvirus 4, Human/isolation & purification , Humans , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Lymphoma, Large B-Cell, Diffuse/diagnostic imaging , Male , Middle Aged , Tomography, X-Ray Computed
6.
Neuroscience ; 142(4): 999-1004, 2006 Nov 03.
Article in English | MEDLINE | ID: mdl-16996221

ABSTRACT

The neurons of the lateral hypothalamus that contain hypocretin/orexin (hcrt/orx) are thought to promote arousal through the excitatory action they exert on the multiple areas to which they project within the CNS. We show here that the hcrt/orx peptides can also exert a strong action on the amygdala, a structure known for its implication in emotional aspects of behavior. Indeed, the hcrt/orx peptides, applied in acute rat brain slices, excite a specific class of "low threshold burst" neurons in the central medial (CeM) nucleus which is considered as a major output of the amygdala. These excitatory effects are postsynaptic, mediated by Hcrt2/OX2 receptors and result from the closure of a potassium conductance. They occur on a class of neurons that are also excited by vasopressin acting through V1a receptors. These results suggest that the hcrt/orx system can act through the amygdala to augment arousal and evoke the autonomic and behavioral responses associated with fear, stress or emotion.


Subject(s)
Amygdala/metabolism , Excitatory Postsynaptic Potentials/physiology , Intracellular Signaling Peptides and Proteins/metabolism , Neural Pathways/metabolism , Neurons/metabolism , Neuropeptides/metabolism , Synaptic Transmission/physiology , Action Potentials/drug effects , Action Potentials/physiology , Amygdala/drug effects , Animals , Arousal/drug effects , Arousal/physiology , Excitatory Postsynaptic Potentials/drug effects , Fear/drug effects , Fear/physiology , Intracellular Signaling Peptides and Proteins/pharmacology , Neural Pathways/drug effects , Neurons/drug effects , Neuropeptides/pharmacology , Orexin Receptors , Orexins , Organ Culture Techniques , Potassium Channels/drug effects , Potassium Channels/metabolism , Rats , Receptors, G-Protein-Coupled/drug effects , Receptors, G-Protein-Coupled/metabolism , Receptors, Neuropeptide/drug effects , Receptors, Neuropeptide/metabolism , Receptors, Vasopressin/agonists , Receptors, Vasopressin/metabolism , Stress, Psychological/metabolism , Stress, Psychological/physiopathology , Synaptic Transmission/drug effects , Vasopressins/metabolism , Vasopressins/pharmacology
7.
Prostate Cancer Prostatic Dis ; 9(3): 279-83, 2006.
Article in English | MEDLINE | ID: mdl-16702984

ABSTRACT

OBJECTIVE: Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed. PATIENTS AND METHODS: Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time. RESULTS: In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022). CONCLUSIONS: During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.


Subject(s)
Androgen Antagonists/therapeutic use , Biomarkers, Tumor/analysis , Carcinoma/drug therapy , Prostatic Neoplasms/drug therapy , Aged , Aged, 80 and over , Anilides/administration & dosage , Anilides/therapeutic use , Antineoplastic Combined Chemotherapy Protocols , Biopsy , Carcinoma/diagnosis , Carcinoma/pathology , Cell Proliferation , Gene Expression Regulation, Neoplastic , Goserelin/administration & dosage , Goserelin/therapeutic use , Humans , Male , Middle Aged , Neoplasm Staging , Nitriles , Prognosis , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Testosterone/blood , Tosyl Compounds , Withholding Treatment
8.
Neuroscience ; 130(4): 807-11, 2005.
Article in English | MEDLINE | ID: mdl-15652980

ABSTRACT

Hypocretin/orexin (Hcrt/Orx) and melanin concentrating hormone (MCH) are peptides contained in overlapping cell groups of the lateral hypothalamus and commonly involved in regulating sleep-wake states and energy balance, though likely in different ways. To see if these neurons are similarly or differentially modulated by neurotransmitters of the major brainstem arousal systems, the effects of noradrenaline (NA) and carbachol, a cholinergic agonist, were examined on identified Hcrt/Orx and MCH neurons in rat hypothalamic slices. Whereas both agonists depolarized and excited Hcrt/Orx neurons, they both hyperpolarized MCH neurons by direct postsynaptic actions. According to the activity profiles of the noradrenergic locus coeruleus and cholinergic pontomesencephalic neurons across the sleep-waking cycle, the Hcrt/Orx neurons would be excited by NA and acetylcholine (ACh) and thus active during arousal, whereas the MCH neurons would be inhibited by NA and ACh and thus inactive during arousal while disinhibited and possibly active during slow wave sleep. According to the present pharmacological results, Hcrt/Orx neurons may thus stimulate arousal in tandem with other arousal systems, whereas MCH neurons may function in opposition with other arousal systems and thus potentially dampen arousal to promote sleep.


Subject(s)
Acetylcholine/physiology , Hypothalamic Area, Lateral/metabolism , Hypothalamic Hormones/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Melanins/metabolism , Neurons/metabolism , Neuropeptides/metabolism , Norepinephrine/physiology , Pituitary Hormones/metabolism , Acetylcholine/pharmacology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Arousal/drug effects , Arousal/physiology , Cholinergic Agonists/pharmacology , Hypothalamic Area, Lateral/cytology , Hypothalamic Area, Lateral/drug effects , Locus Coeruleus/physiology , Models, Neurological , Neural Inhibition/drug effects , Neural Inhibition/physiology , Neural Pathways/cytology , Neural Pathways/drug effects , Neural Pathways/metabolism , Neurons/drug effects , Norepinephrine/pharmacology , Orexins , Organ Culture Techniques , Patch-Clamp Techniques , Pedunculopontine Tegmental Nucleus/physiology , Rats , Rats, Sprague-Dawley , Sleep/physiology , Synaptic Transmission/drug effects , Synaptic Transmission/physiology
9.
Behav Brain Res ; 133(2): 185-96, 2002 Jul 18.
Article in English | MEDLINE | ID: mdl-12110452

ABSTRACT

The present study was designed to test whether prenatal cocaine (COC) exposure alters sensitivity to the attentional effects of idazoxan (IDZ), an alpha-2 adrenergic antagonist that increases coeruleocortical NE activity. The task assessed subjects' ability to selectively attend to an unpredictable light cue and disregard olfactory distractors. IDZ increased commission errors specifically under conditions of distraction, an effect that was similar in the COC and control groups. In contrast, COC animals were significantly more sensitive than controls to the effects of IDZ on omission errors and nontrials. The pattern of effects suggests that the differential treatment response to IDZ on these latter measures resulted from an alteration in norepinephrine (NE)-modulated dopamine release in the COC animals, reflecting lasting changes in dopaminergic and/or noradrenergic systems as a result of the early cocaine exposure. Based on the behavioral measures that showed a differential response to IDZ in the COC animals, it seems likely that these changes may contribute to the alterations in sustained attention and arousal regulation that have been reported in both animals and humans exposed to cocaine in utero.


Subject(s)
Adrenergic alpha-Antagonists/pharmacology , Attention/drug effects , Cocaine/toxicity , Idazoxan/pharmacology , Animals , Female , Injections, Intravenous , Pregnancy , Prenatal Exposure Delayed Effects , Psychomotor Performance/drug effects , Rats , Rats, Long-Evans
10.
Neuroscience ; 108(2): 177-81, 2001.
Article in English | MEDLINE | ID: mdl-11734353

ABSTRACT

The orexins (orexin A and B, also known as hypocretin 1 and 2) are two recently identified neuropeptides (de Lecea et al., 1998; Sakurai et al., 1998) which are importantly implicated in the control of wakefulness (for reviews see Hungs and Mignot, 2001; van den Pol, 2000; Willie et al., 2001 ). Indeed, alteration in these peptides' precursor, their receptors or the hypothalamic neurones that produce them leads to the sleep disorder narcolepsy (Chemelli et al., 1999; Lin et al., 1999; Peyron et al., 2000; Thannickal et al., 2000). The mechanisms by which the orexins modulate wakefulness, however, are still unclear. Their presence in fibres coursing from the hypothalamus (Peyron et al., 1998) up to the preoptic area (POA) and basal forebrain (BF) suggests that they might influence the important sleep and waking neural systems situated there (Jones, 2000). The present study, performed in rat brain slices, demonstrates, however, that the orexins have no effect on the GABA sleep-promoting neurones of the POA, whereas they have a strong and direct excitatory effect on the cholinergic neurones of the contiguous BF. In addition, by comparing the effects of orexin A and B we demonstrate here that orexins' action depends upon orexin type 2 receptors (OX(2)), which are those lacking in narcoleptic dogs (Lin et al., 1999). These results suggest that the orexins excite cholinergic neurones that release acetylcholine in the cerebral cortex and thereby contribute to the cortical activation associated with wakefulness.


Subject(s)
Acetylcholine/metabolism , Basal Nucleus of Meynert/metabolism , Biotin/analogs & derivatives , Carrier Proteins/metabolism , Cholinergic Fibers/metabolism , Intracellular Signaling Peptides and Proteins , Neurons/metabolism , Neuropeptides/metabolism , Wakefulness/physiology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Basal Nucleus of Meynert/cytology , Basal Nucleus of Meynert/drug effects , Carrier Proteins/pharmacology , Cholinergic Fibers/drug effects , Cholinergic Fibers/ultrastructure , Dose-Response Relationship, Drug , Neural Inhibition/drug effects , Neural Inhibition/physiology , Neurons/cytology , Neurons/drug effects , Neuropeptides/pharmacology , Orexin Receptors , Orexins , Organ Culture Techniques , Preoptic Area/cytology , Preoptic Area/drug effects , Preoptic Area/metabolism , Rats , Receptors, G-Protein-Coupled , Receptors, Neuropeptide/drug effects , Receptors, Neuropeptide/metabolism , Wakefulness/drug effects , gamma-Aminobutyric Acid/metabolism
11.
Eur J Neurosci ; 14(9): 1571-5, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11722619

ABSTRACT

Wakefulness has recently been shown to depend upon the newly identified orexin (or hypocretin) neuropeptides by the findings that alteration in their precursor protein, their receptors or the neurons that produce them leads to the sleep disorder narcolepsy in both animals and humans. The questions of how and where these brain peptides act to maintain wakefulness remain unresolved. The purpose of the present study was to determine whether the orexins could directly affect hypothalamic histaminergic neurons, which are known to contribute to the state of wakefulness by their diffuse projections through the brain. Using brain slices, we recorded in the ventral tuberomammillary nuclei from neurons identified as histaminergic on the basis of their previously described morphological and electrophysiological characteristics and found that they were depolarized and excited by the orexins through a direct postsynaptic action. We then compared the depolarizing effect of orexin A and B and found that they were equally effective upon these cells. This latter finding suggests that the effect of orexins is mediated by orexin type 2 receptors, which are those lacking in narcoleptic dogs. Our results therefore show that the histaminergic neurons of the tuberomammillary nuclei represent an important target for the orexin system in the maintenance of wakefulness.


Subject(s)
Action Potentials/drug effects , Biotin/analogs & derivatives , Carrier Proteins/pharmacology , Histamine/metabolism , Hypothalamic Area, Lateral/drug effects , Intracellular Signaling Peptides and Proteins , Neurons/drug effects , Neuropeptides/pharmacology , Wakefulness/drug effects , Action Potentials/physiology , Animals , Carrier Proteins/metabolism , Efferent Pathways/cytology , Efferent Pathways/drug effects , Efferent Pathways/metabolism , Hypothalamic Area, Lateral/cytology , Hypothalamic Area, Lateral/metabolism , Molecular Probes , Narcolepsy/metabolism , Narcolepsy/pathology , Narcolepsy/physiopathology , Neurons/cytology , Neurons/metabolism , Neuropeptides/metabolism , Orexins , Organ Culture Techniques , Rats , Synapses/drug effects , Synapses/metabolism , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Wakefulness/physiology
12.
Exp Neurol ; 168(2): 259-72, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11259114

ABSTRACT

In diabetes, increased oxidative stress, disruption of signal transduction pathways, and endothelial dysfunction have been critically implicated in the pathogenesis of experimental diabetic neuropathy (EDN). The development of nerve conduction slowing in diabetes is accompanied by depletion of the beta-amino acid taurine. Since taurine functions as an antioxidant, calcium modulator, and vasodilator, taurine depletion may provide a pathogenetic link between nerve metabolic, vascular, and functional deficits complicating diabetes. The mechanism(s) of nerve taurine depletion, the localization of critical taurine deficits, and its pathophysiological significance in EDN are however unknown. This study explored the pathophysiological effects of selective nerve taurine replacement in streptozotocin-diabetic (STZ-D) rats. A polyclonal human taurine transporter (TT) antibody was also generated in order to determine potential loci of critical taurine depletion. Two weeks of STZ-D reduced sciatic motor nerve conduction velocity (NCV) by 23% (P < 0.01), decreased composite nerve blood flow by 38% (P < 0.01), and reduced nerve taurine content by 29% (P < 0.05). In STZ-D rats, a 1% taurine diet corrected nerve taurine depletion, prevented motor NCV slowing, and partially attenuated composite nerve blood flow deficits. After 6 weeks of STZ-D, a 1% taurine diet ameliorated motor NCV slowing and endoneurial nutritive blood flow deficits, prevented digital sensory NCV slowing, and reduced ouabain-sensitive nerve (Na,K)-ATPase activity. Immunohistochemical studies localized taurine and the TT to the vascular endothelium and Schwann cells of the sciatic nerve. In conclusion, taurine depletion in the vascular endothelium and Schwann cells of the sciatic nerve may contribute to the neurovascular and metabolic deficits in EDN.


Subject(s)
Carrier Proteins/metabolism , Diabetes Mellitus, Experimental/metabolism , Diabetic Neuropathies/metabolism , Membrane Glycoproteins/metabolism , Membrane Transport Proteins , Neural Conduction/physiology , Sciatic Nerve/metabolism , Taurine/metabolism , Animals , Anti-Bacterial Agents , Blood Flow Velocity/drug effects , Blood Flow Velocity/physiology , Blood Glucose/drug effects , Blood Glucose/physiology , Blood Pressure/drug effects , Blood Pressure/physiology , Body Weight/drug effects , Body Weight/physiology , Diabetes Mellitus, Experimental/physiopathology , Diabetic Neuropathies/physiopathology , Endothelium, Vascular/metabolism , Humans , Male , Neural Conduction/drug effects , Rabbits , Rats , Rats, Wistar , Sciatic Nerve/blood supply , Sciatic Nerve/drug effects , Streptozocin , Taurine/pharmacology
13.
Cancer ; 89(10): 2117-21, 2000 Nov 15.
Article in English | MEDLINE | ID: mdl-11066053

ABSTRACT

BACKGROUND: In the past, patients with metastatic retinoblastoma have had a poor prognosis when treated with conventional modalities. In the current study, the authors evaluated the use of combined intensive conventional chemotherapy, high dose chemotherapy with autologous stem cell rescue (ASCR), and radiation therapy. METHODS: Four patients with metastatic retinoblastoma were treated. All had orbital and bone marrow metastases. In addition, three patients had bone metastases and two patients had liver metastases. None had central nervous system disease. Patients received intensive conventional chemotherapy that included vincristine, cyclophosphamide, etoposide, and either cisplatin or carboplatin. Stem cells were harvested after bone marrow disease was no longer detectable. High dose chemotherapy with carboplatin (500 mg/m(2)/day x 3 days or area under the curve = 7 via the Calvert formula) and thiotepa (300 mg/m(2)/day x 3 days) with (n = 3 patients) or without (n = 1 patient) etoposide (250 mg/m(2)/day x 3 days) was administered with ASCR. Sites that originally harbored bulky disease were irradiated after recovery from the high dose chemotherapy. RESULTS: The therapy was associated with substantial acute hematopoietic and mucosal toxicities. At last follow-up, all four patients had survived event free from 46-80 months after the diagnosis of metastatic disease. CONCLUSIONS: The treatment strategy described in the current study is effective for patients with metastatic retinoblastoma that does not involve the central nervous system. However, a multicenter trial should be considered to evaluate it in a larger group of patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Bone Marrow Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Retinal Neoplasms/therapy , Retinoblastoma/therapy , Adolescent , Adult , Antineoplastic Agents/adverse effects , Bone Marrow Neoplasms/secondary , Combined Modality Therapy , Female , Follow-Up Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Retinal Neoplasms/mortality , Retinal Neoplasms/pathology , Retinal Neoplasms/radiotherapy , Retinoblastoma/mortality , Retinoblastoma/radiotherapy , Retinoblastoma/secondary , Survival Analysis , Treatment Outcome
14.
J Clin Pharmacol ; 40(6): 624-33, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10868313

ABSTRACT

The possibility of an effect of ethnicity on the pharmacokinetics of mycophenolic acid, the immunosuppressive metabolite of the prodrug mycophenolate mofetil, was studied over 90 days following renal transplantation in African American (n = 13) and Caucasian patients (n = 20). Since renal dysfunction and time after transplant surgery are two factors known to alter mycophenolic acid pharmacokinetics, two-way analysis of variance of the data at each time point with ethnicity and renal function status as covariates was used to evaluate the possibility of an ethnicity effect on the pharmacokinetic parameters. No statistically significant difference based on ethnicity was detected for the primary pharmacokinetic parameters, abbreviated mycophenolic acid area under the concentration-time curve (MPA AUC), or the predose trough concentration on study days 4, 7, 14, 28, or 90. A statistically significant decrease in MPA AUC and increase in oral apparent clearance were observed in renally impaired patients regardless of ethnicity on days 4, and 4 and 7, respectively. The suggested mechanism for these differences is uremia-induced increased MPA free fraction, leading to a temporary increased clearance for this restrictively cleared drug.


Subject(s)
Immunosuppressive Agents/pharmacokinetics , Kidney Transplantation , Mycophenolic Acid/pharmacokinetics , Adult , Aged , Area Under Curve , Black People , Female , Humans , Male , Metabolic Clearance Rate , Middle Aged , White People
15.
Hepatogastroenterology ; 47(32): 554-5, 2000.
Article in English | MEDLINE | ID: mdl-10791236

ABSTRACT

The authors report the case of a 45-year-old woman who suffered from epigastric pain and was operated on 3 years before for colon cancer. The clinical investigation revealed that the patient had colon cancer metastasis to the dorsal pancreas of a pancreas divisum.


Subject(s)
Colonic Neoplasms/surgery , Pancreas/abnormalities , Pancreatic Neoplasms/secondary , Cholangiopancreatography, Endoscopic Retrograde , Colonic Neoplasms/pathology , Female , Humans , Middle Aged , Pancreas/pathology , Pancreatectomy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery
16.
J Perinatol ; 20(2): 129-31, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10785890

ABSTRACT

An increased fetal nuchal translucency detected by first trimester ultrasound has been associated with an elevated risk of aneuploidy. The etiology of the increased nuchal translucency in fetuses with normal chromosomes is uncertain, but it has been associated with poor pregnancy outcome. We report a fetus with increased nuchal translucency and a normal karyotype, in which parvovirus was detected by polymerase chain reaction in the amniotic fluid. Although an ultrasound detected an increased nuchal fold thickness in the second trimester, the pregnancy was otherwise uncomplicated. Parvovirus should be considered as a possible etiology of increased nuchal translucency. The risks to a fetus with first trimester parvovirus infections diagnosed under these conditions are uncertain and require larger studies.


Subject(s)
Neck/diagnostic imaging , Parvoviridae Infections/diagnostic imaging , Parvovirus , Ultrasonography, Prenatal , Adult , Amniotic Fluid/virology , Female , Humans , Parvovirus/isolation & purification , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, First , Pregnancy Trimester, Second
17.
Bone ; 26(2): 111-6, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10678404

ABSTRACT

The polymorphisms of the estrogen receptor (ER) gene defined by the restriction enodonucleases PvuII and XbaI have recently been reported to be associated with bone mineral density (BMD) in postmenopausal women. To investigate the possible relation of the PvuII and XbaI restriction fragment-length polymorphisms of the ER gene with BMD in Danish postmenopausal women, two studies were undertaken: 1) a cross-sectional study of 499 postmenopausal women, where the ER genotypes and alleles were related to BMD of the hip, spine, and lower forearm; and 2) a longitudinal study of 101 postmenopausal women followed up for 18 years. In the latter study, late postmenopausal bone loss in the hip and spine was determined over a period of 6 years in women (mean age of 63 to 69 years), and long-term postmenopausal bone loss in the lower forearm was determined over a period of 18 years in women (mean age of 51 to 69 years). Genotyping was performed through the restriction cleavage of polymerase chain reaction-amplified genomic DNA with the two restriction enzymes, PvuII and XbaI. Restriction fragment-length polymorphisms were represented as P or p (PvuII) and X or x (XbaI), with the lower case letters signifying the presence of the restriction site. The frequencies of the ER genotypes were similar to previously published genotype frequencies in Caucasian and Asian populations. No significant effect of the ER genotypes or alleles on BMD was found at any site, nor was there a relation between ER genotypes and the rate of bone loss either in the hip and spine over 6 years, or in the lower forearm over 18 years. In conclusion, we could not demonstrate any major effect of the ER gene polymorphisms on BMD or rate of bone loss in healthy postmenopausal Danish women.


Subject(s)
Bone Density/genetics , Bone Density/physiology , Osteoporosis, Postmenopausal/genetics , Osteoporosis, Postmenopausal/metabolism , Polymorphism, Restriction Fragment Length , Receptors, Estrogen/genetics , Aged , Alleles , Base Sequence , Cross-Sectional Studies , DNA Primers/genetics , Denmark , Estrogen Replacement Therapy , Female , Genotype , Humans , Longitudinal Studies , Middle Aged
18.
Neuroreport ; 11(3): 531-3, 2000 Feb 28.
Article in English | MEDLINE | ID: mdl-10718309

ABSTRACT

Following an i.p. injection of 2-deoxyglucose (2DG), a nonmetabolizable analogue of glucose known to induce intracellular glucopenia, a progressive decrease in the level of hypocretin (Hcrt)/orexin mRNA was observed in the rat lateral hypothalamus while the melanin-concentrating hormone (MCH) expression in neighbouring neurons remained unaffected. This result together with the previously reported stimulation of Hcrt expression by insulin confirms that Hcrt neurons, but not MCH neurons, are sensitive to glucose availability and suggests that they respond through different mechanisms and/or different pathways to intracellular glucopenia and hypoglycemic conditions.


Subject(s)
Carrier Proteins , Deoxyglucose/pharmacology , Gene Expression/drug effects , Hypothalamic Area, Lateral/physiology , Intracellular Signaling Peptides and Proteins , Neuropeptides , Neurotransmitter Agents/genetics , Animals , Blood Glucose/analysis , Hypothalamic Area, Lateral/cytology , Hypothalamic Hormones/genetics , Hypothalamic Hormones/metabolism , Immunohistochemistry , In Situ Hybridization , Male , Melanins/genetics , Melanins/metabolism , Neurons/metabolism , Neurons/physiology , Neurotransmitter Agents/metabolism , Orexins , Pituitary Hormones/genetics , Pituitary Hormones/metabolism , Rats , Rats, Sprague-Dawley , Time Factors
19.
Injury ; 31(4): 243-8, 2000 May.
Article in English | MEDLINE | ID: mdl-10719103

ABSTRACT

Occult fractures of the scaphoid bone occur frequently and may lead to non-union. The use of three-phase bone scintigraphy in patients with normal x-rays of the scaphoid after carpal injury is widely advocated.In this study, 40 patients with negative radiographs but clinically suspected scaphoid fracture, all had rapid bone scintigraphy with images taken 15 min after intravenous injection of 99 m-Technetium Hydroxymethylene diphosphonate. The scan was performed approximately 2 weeks after the trauma. We found 8 fractures of the scaphoid bone and 13 fractures of other carpal bones. In 5 cases the images were inconclusive. At follow-up 6 months to 2 years later we found no patients with non-union. We find this rapid version of the bone scan useful as a second line investigation for continuing wrist pain following trauma in the presence of normal radiography. This can result in a reduction in both time and costs required for the diagnostic process. If the results are inconclusive we recommend a delayed image. CT or MRI could also be considered. In rare cases a wrist arthroscopy may be considered.


Subject(s)
Fractures, Bone/diagnostic imaging , Adolescent , Adult , Child , Diphosphonates , Female , Humans , Male , Middle Aged , Organotechnetium Compounds , Pain/etiology , Radiography , Radionuclide Imaging , Radiopharmaceuticals , Retrospective Studies , Surveys and Questionnaires , Time Factors
20.
J Neurosci ; 20(23): 8902-8, 2000 Dec 01.
Article in English | MEDLINE | ID: mdl-11102500

ABSTRACT

Sensitivity to the attentional effects of SKF81297, a selective full agonist at dopamine D(1) receptors, was assessed in adult rats exposed to cocaine prenatally (via intravenous injections) and controls. The task assessed the ability of the subjects to monitor an unpredictable light cue of either 300 or 700 msec duration and to maintain performance when presented with olfactory distractors. SKF81297 decreased nose pokes before cue presentation and increased latencies and response biases (the tendency to respond to the same port used on the previous trial), suggesting an effect of SKF81297 on the dopamine (DA) systems responsible for response initiation and selection. The cocaine-exposed (COC) and control animals did not differ in sensitivity to the effects of SKF81297 on these measures. In contrast, the COC animals were significantly more sensitive than were controls to the impairing effect of SKF81297 on omission errors, a measure of sustained attention. This pattern of results provides evidence that prenatal cocaine exposure produces lasting changes in the DA system(s) subserving sustained attention but does not alter the DA system(s) underlying response selection and initiation. These findings also provide support for the role of D(1) receptor activation in attentional functioning.


Subject(s)
Attention/drug effects , Benzazepines/pharmacology , Cocaine/administration & dosage , Prenatal Exposure Delayed Effects , Receptors, Dopamine D1/agonists , Animals , Attention/physiology , Behavior, Animal/drug effects , Cues , Discrimination Learning/drug effects , Dopamine Agonists/pharmacology , Dose-Response Relationship, Drug , Female , Injections, Intravenous , Male , Photic Stimulation , Pregnancy , Rats , Rats, Long-Evans , Reaction Time/drug effects , Smell/drug effects
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