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1.
Br J Surg ; 106(12): 1666-1675, 2019 11.
Article in English | MEDLINE | ID: mdl-31639208

ABSTRACT

BACKGROUND: Pain is a common debilitating symptom in pancreatic adenocarcinoma. This cohort study examined the use of, and factors associated with, pain-directed interventions for a high pain score in patients with non-curable pancreatic adenocarcinoma. METHODS: Administrative databases were linked and patients with non-resected pancreatic adenocarcinoma diagnosed between 2010 and 2016, who reported one or more Edmonton Symptom Assessment System (ESAS) score, were identified. A high pain score was defined as an ESAS score of at least 4. Outcomes were pain-directed interventions: opiates (in patients aged 65 years or more with universal drug coverage), nerve block and radiation therapy for a high pain score. Reduction in pain score of at least 1 point after pain-directed intervention was also evaluated. Modified Poisson regression was used to examine factors associated with pain-directed intervention. RESULTS: Among 2623 patients with a median age of 67 years, 1223 (46·6 per cent) were women, and 1621 (61·8 per cent) reported a high pain score at a median of 38 days after diagnosis. Of those with a high pain score, 75·6 per cent (688 of 910) received opiates, 13·5 per cent (219 of 1621) radiation and 1·2 per cent (19 of 1621) nerve block. The pain score decreased in 62·1 per cent of patients after administration of opiates, 73·4 per cent after radiation and all patients after nerve block. In multivariable analysis, no patient factor (age, sex, co-morbidity burden, rurality, income quintile) was associated with receipt of non-opiate pain-directed intervention for a high pain score. In patients aged at least 65 years, advanced age was associated with lower odds of opiate use. CONCLUSION: Opiates are the most common pain-directed intervention for non-curable pancreatic adenocarcinoma, whereas radiation therapy and nerve blocks are seldom used. The lack of association between pain-directed interventions and patient factors points toward practice-driven patterns.


ANTECEDENTES: El dolor es un síntoma debilitante frecuente en el adenocarcinoma de páncreas. Este estudio de cohortes examinó el uso de las intervenciones dirigidas para el tratamiento del dolor y los factores asociados a las mismas en pacientes con adenocarcinoma pancreático incurable que presentaban puntuaciones altas de dolor. MÉTODOS: Se revisaron las bases de datos administrativas y se identificaron los pacientes con adenocarcinoma pancreático no resecado diagnosticados entre 2010-2016 con puntuaciones > 1 del Sistema de Evaluación de Síntomas de Edmonton (Edmonton Symptom Assessment System, ESAS). La puntuación alta de dolor se definió como ESAS > 4. Los resultados evaluados fueron las intervenciones dirigidas contra el dolor: opiáceos (en pacientes mayores de 65 años con cobertura universal de medicamentos), bloqueo nervioso y radioterapia en el caso de puntuación alta del dolor. También se evaluó la reducción en la puntuación del dolor (> 1 punto) después de la intervención dirigida contra el dolor. Los factores asociados a la intervención contra el dolor se analizaron mediante una regresión de Poisson modificada. RESULTADOS: De los 2.623 pacientes con una mediana de edad de 67 años, 1.223 (46,6%) eran mujeres, y 1.621 (61.8%) presentaron una puntuación alta de dolor con una mediana de 38 días desde el momento del diagnóstico. De aquellos con puntuación alta de dolor, el 75,6% recibió opiáceos (n = 688/910), el 13,5% radiación (n = 219/1.621) y el 1,2% bloqueo nervioso (n = 19/1.621). La puntuación del dolor disminuyó en el 62,2% después del tratamiento con los opiáceos, en el 73,8% después de la radiación y en el 100% después del bloqueo nervioso. En el análisis multivariable, ningún factor relacionado con el paciente (edad, sexo, comorbilidades, vivir en una zona rural, quintil de ingresos) se asoció con una intervención dirigida contra dolor sin opiáceos en los casos de puntuación alta del dolor. En pacientes mayores de 65 años, la edad avanzada se asoció con menor probabilidad de uso de opiáceos. CONCLUSIÓN: Mientras que los opiáceos son la intervención dirigida contra dolor más común para el adenocarcinoma pancreático no resecable, la radioterapia y el bloqueo nervioso rara vez se usan. La falta de asociación de las intervenciones dirigidas contra el dolor con los factores del paciente apunta hacia el uso de patrones terapéuticos basados ​​en la práctica clínica.


Subject(s)
Adenocarcinoma/physiopathology , Cancer Pain/diagnosis , Cancer Pain/therapy , Pancreatic Neoplasms/physiopathology , Age Factors , Aged , Aged, 80 and over , Analgesics, Opioid/therapeutic use , Cancer Pain/etiology , Female , Humans , Male , Middle Aged , Nerve Block , Pain Measurement , Radiotherapy , Retrospective Studies , Self Report
2.
Curr Oncol ; 26(1): e8-e16, 2019 02.
Article in English | MEDLINE | ID: mdl-30853804

ABSTRACT

Purpose: Patient-reported symptom data are collected prospectively by a provincial cancer agency to mitigate the significant symptom burden that patients with cancer experience. However, an assessment of whether such symptom screening occurs uniformly for those patients has yet to be performed. In the present study, we investigated patient, disease, and health system factors associated with receipt of symptom screening in the year after a cancer diagnosis. Methods: Patients diagnosed with cancer between 2007 and 2014 were identified. We measured whether 1 or more symptom screenings were recorded in the year after diagnosis. A multivariable modified Poisson regression with robust error variance was used to identify predictors [age, comorbidity, rurality, socioeconomic status, immigration status, cancer site, registration at a regional cancer centre (cc), and year of diagnosis] of being screened for symptoms. Results: Of 425,905 patients diagnosed with cancer, 163,610 (38%) had 1 or more symptom screening records in the year after diagnosis, and 75% survived at least 1 year. We identified variability in symptom screening by primary cancer site, regional cc, age, sex, comorbidity, material deprivation, rurality of residence, and immigration status. Patients who had been diagnosed with melanoma or endocrine cancers, who were not registered at a regional cc, who lived in the most urban areas, who were elderly, and who were immigrants were least likely to undergo symptom screening after diagnosis. Conclusions: Our evaluation of the implementation of a population-based symptom screening program in a universal health care system identified populations who are at risk for not receiving screening and who are therefore future targets for improvements in population symptom screening and better management of cancer-related symptoms at diagnosis.


Subject(s)
Early Detection of Cancer/methods , Neoplasms/epidemiology , Patient Reported Outcome Measures , Universal Health Care , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Mass Screening , Middle Aged , Retrospective Studies , Risk Factors , Young Adult
4.
Acta Physiol (Oxf) ; 194(4): 325-34, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18729844

ABSTRACT

AIMS: We investigated whether chronic fetal anaemia affects myocardial infarct in adulthood and elicits functional modifications in adult coronary vasoreactivity. METHODS: Seven-month-old sheep that were made anaemic in utero and transfused to normal haematocrit before birth were studied. Infarct size was determined by tetrazolium after 1-h ischaemia (occlusion of the mid of left anterior descending artery) and 2-h reperfusion. The dose-response to vasoconstrictors and vasodilators was assessed in small resistance coronary arteries. RESULTS: There were no significant differences between the animals previously subjected to in utero anaemia and the control animals regarding the percentage infarct size and the area-at-risk to the left ventricle. The ventricular function (dP/dt) was preserved. The percentage infarct size of the area-at-risk (70.7 +/- 3.5%) was larger than that in the controls (49.8 +/- 4.5%) (P = 0.006). The vascular responses were not altered. Endothelium-dependent relaxation to bradykinin (96.0 +/- 2.6% vs. 98.8 +/- 1.0%) was not affected by PGI(2) inhibitor (94.6 +/- 2.6% vs. 98.5 +/- 1.0%) but significantly reduced by the inhibition of nitric oxide (NO) in both anaemic (P < 0.05) and control (P < 0.001) groups with a significant right shift of EC(50) (P < 0.01). The non-NO-non-PGI(2)-mediated relaxation was slightly potentiated in anaemic animals. CONCLUSIONS: Exposing fetal sheep to in utero anaemia in late gestation for 3 weeks may increase the susceptibility of adult hearts to ischaemia-reperfusion injury without major alterations in coronary vasomotor responsiveness. The impact of in utero anaemia at earlier period of pregnancy and on the earlier or later life of the adult is yet to be further investigated.


Subject(s)
Anemia/embryology , Myocardial Infarction/epidemiology , Myocardial Reperfusion Injury/embryology , 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology , Animals , Cardiovascular Agents/pharmacology , Chronic Disease , Indomethacin/pharmacology , Sheep , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effects , Vasodilator Agents/pharmacology
5.
Lab Anim ; 42(3): 326-30, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18625587

ABSTRACT

Two anaesthetic protocols were compared using pregnant sheep. In both groups of animals, anaesthesia was induced using an intravenous (i.v.) injection of diazepam and ketamine. The ewes were then intubated for positive pressure ventilation using 0.8 L/min of nitrous oxide and 2 L/min oxygen with 1.1-1.8% halothane. If the ewe showed any signs of awakening, one of two protocols was followed. First, the halothane concentration was increased to 2-3% until the ewe was completely anaesthetized. Second, the halothane concentration was not altered, but the ewe was given doses of i.v. diazepam (0.1 mg/kg) and ketamine (1 mg/kg) until again completely anaesthetized. At the completion of surgery, maternal recovery was rapid and similar between the two groups. However, five days after surgery, the fetal arterial Po(2) and oxygen content of the fetuses receiving additional halothane (1.9 +/- 0.2 kPa and 4.4 +/- 1.0 mL/100 mL) were statistically significantly depressed when compared with the fetuses receiving additional diazepam and ketamine (2.9 +/- 0.1 kPa and 7.0 +/- 0.5 mL/100 mL). These results led us to conclude that certain anaesthetic protocols, in spite of good maternal recovery, can lead to deleterious effects upon the fetus that persist for at least five days after surgery.


Subject(s)
Anesthesia/methods , Blood Gas Analysis , Models, Animal , Sheep/blood , Anesthesia/adverse effects , Anesthetics/pharmacology , Animals , Blood Pressure/drug effects , Blood Pressure/physiology , Carbon Dioxide/blood , Diazepam/pharmacology , Female , Fetus , Halothane/adverse effects , Halothane/pharmacology , Heart Rate, Fetal/drug effects , Heart Rate, Fetal/physiology , Ketamine/pharmacology , Oxygen/blood , Pregnancy , Sheep/embryology , Sheep/surgery
6.
Placenta ; 27(8): 876-81, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16289267

ABSTRACT

Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (P<0.0001). Fetal arterial blood pressures rose from 42+/-3 to 59+/-4 mmHg (P<0.01) and venous pressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (P<0.01). In spite of the large increase in driving pressure, fetal placental blood flow remained (statistically) constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (P<0.01). On day 7, plasma renin activity had fallen from 6.7+/-4.2 ng/(ml/h) at preinfusion control to 0.6+/-0.6 ng/(ml/h) (P<0.05) and plasma angiotensin-II concentration had fallen from 33.2+/-26.6 to 6.2+/-3.9 pg/ml, although this fall was not statistically significant (P=0.07). Fetal placental flow did not increase with increased driving pressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow.


Subject(s)
Blood Transfusion, Intrauterine , Fetus/physiology , Placental Circulation/physiology , Umbilical Arteries/physiology , Vascular Resistance/physiology , Animals , Blood Pressure/physiology , Blood Proteins/analysis , Female , Infusions, Intra-Arterial , Plasma , Pregnancy , Renin/blood , Sheep, Domestic
7.
N Engl J Med ; 352(22): 2271-84, 2005 Jun 02.
Article in English | MEDLINE | ID: mdl-15930418

ABSTRACT

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.


Subject(s)
Chickenpox Vaccine , Herpes Zoster/prevention & control , Herpesvirus 3, Human , Neuralgia/prevention & control , Aged , Chickenpox Vaccine/adverse effects , Chickenpox Vaccine/immunology , Cost of Illness , Double-Blind Method , Female , Follow-Up Studies , Herpes Zoster/complications , Herpes Zoster/epidemiology , Herpesvirus 3, Human/immunology , Humans , Immunologic Memory , Incidence , Male , Middle Aged , Neuralgia/virology , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/immunology , Virus Activation
9.
Neurology ; 63(6): 1070-7, 2004 Sep 28.
Article in English | MEDLINE | ID: mdl-15452300

ABSTRACT

BACKGROUND: The prevalence of symptoms suggesting distal symmetric polyneuropathy (DSP) was reported to be higher among deployed veterans (DV) to the Persian Gulf in 1990-1991 than to control non-deployed veterans (NDV). The authors therefore compared the prevalence of DSP by direct examination of DV and their spouses to control NDV and spouses. METHODS: The authors performed standardized neurologic examinations on 1,061 DV and 1,128 NDV selected from a cohort of veterans who previously participated in a national mail and telephone survey. Presence of DSP was evaluated by history, physical examination, and standardized electrophysiologic assessment of motor and sensory nerves. Similar examinations were performed without electrophysiologic tests in 484 DV spouses and 533 NDV spouses. Statistical analyses were performed with appropriate adjustments for the stratified sampling scheme. RESULTS: No differences between adjusted population prevalence of DSP in DV and NDV were found by electrophysiology (3.7% vs 6.3%, p = 0.07), by neurologic examination (3.1% vs 2.6%, p = 0.60), or by the methods combined (6.3% vs 7.3%, p = 0.47). Excluding veterans with non-military service related diseases that may cause DSP did not alter outcomes. DV potentially exposed to neurotoxins from the Khamisiyah ammunition depot explosion did not significantly differ in DSP prevalence compared to non-exposed DV. The prevalence of DSP in DV spouses did not differ from NDV spouses (2.7% vs 3.2%, p = 0.64). CONCLUSIONS: Neither veterans deployed during the Gulf War era nor their spouses had a higher prevalence of DSP compared to NDV and spouses.


Subject(s)
Electromyography , Neural Conduction , Neurologic Examination , Peripheral Nerves/physiology , Peripheral Nervous System Diseases/epidemiology , Persian Gulf Syndrome/epidemiology , Veterans , Adult , Chemical Warfare Agents/adverse effects , Cohort Studies , Female , Gulf War , History, 17th Century , Humans , Male , Occupational Exposure , Organophosphorus Compounds/adverse effects , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/physiopathology , Persian Gulf Syndrome/diagnosis , Persian Gulf Syndrome/etiology , Persian Gulf Syndrome/physiopathology , Prevalence , Sampling Studies , Spouses
10.
Clin Neurophysiol ; 115(4): 820-33, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15003762

ABSTRACT

OBJECTIVE: Hemiparesis due to damage by stroke in primary motor cortex (MI) or its underlying projections presents a problem for functional neuroimaging technologies that attempt to evaluate the neurophysiological basis for restoration of motor function. Traditional assessments of MI function require patients to move their fingers, hands, or limbs, which can be either impossible or markedly compromised after stroke. We recently demonstrated in normal subjects that magnetoencephalography (MEG), a non-invasive neuromagnetic functional imaging technique, detects neuronal response elicited by electrical median nerve stimulation in MI, as well as primary somatosensory cortex (SI). In the present study, we used the MEG response from median nerve stimulation to investigate the recovery of primary motor and somatosensory in acute ischemic stroke patients. METHODS: Twelve patients with unilateral ischemic strokes that affected sensorimotor functions of their hand were studied in the acute stage (4.4+/-1.2 days, mean+/-SD) and during a 1-month follow-up (38.6+/-5.6 days, except for one patient's follow-up done 6 month after stroke). RESULTS: Among the multiple cortical sources localized after median nerve stimulation, one source localized to SI and another localized to the vicinity of MI. Changes in the source strengths of the first component post-stimulus of MI and SI correlated with the extent of recovery of sensorimotor functions as determined by neurological exams. CONCLUSIONS: This study provides a novel way of indirectly assessing MI function using MEG during the acute stroke phase, when many patients often cannot perform motor tasks due to paralysis.


Subject(s)
Magnetoencephalography , Median Nerve/physiology , Motor Neurons/physiology , Neurons, Afferent/physiology , Stroke/physiopathology , Adult , Aged , Aged, 80 and over , Female , Fingers/innervation , Fingers/physiology , Humans , Male , Median Nerve/cytology , Middle Aged , Reaction Time/physiology
11.
Exp Physiol ; 88(6): 691-8, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14603367

ABSTRACT

Interstitial fluid fluxes are much greater in the fetus than in the adult, and filtration rates are increased over control in most tissues of the anaemic fetus. Increased capillary filtration may lead to cardiac oedema which, in turn, severely impacts cardiac function. Mechanisms that underlie these differences in flux are incompletely understood. One possible mechanism is an increase in capillary water permeability. Therefore, the goal of our study was to determine the level of expression of the water channel aquaporin 1 (AQP1) during cardiac development and in the anaemic fetal sheep heart. Hearts from chronically instrumented anaemic sheep fetuses and hearts from normal early fetal, late fetal, neonatal and adult sheep were used for Northern and Western analyses and immunohistochemistry. We found that AQP1 mRNA levels were lower in the young fetal left ventricle than in the adult left ventricle (P < 0.05). We also found that cardiac AQP1 expression was increased in anaemic fetuses compared to age-matched controls (P < 0.05). Expression of AQP1 in all groups was greatest in the microvascular endothelium. These data suggest that AQP1 plays an important role in the physiological accommodation to fetal anaemia.


Subject(s)
Aging/metabolism , Anemia/metabolism , Aquaporins/metabolism , Heart Ventricles/embryology , Heart Ventricles/metabolism , Myocardium/metabolism , Adaptation, Physiological , Animals , Animals, Newborn , Aquaporin 1 , Female , Sheep
12.
J Dairy Sci ; 86(3): 1029-35, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12703640

ABSTRACT

The Dairy Challenge contest allows undergraduate students to apply knowledge gained in the classroom in an evaluation of the management practices of commercial dairy farms. University faculty partnered with industry representatives to develop the competition. Participants in the Dairy Challenge do the following: 1) critically evaluate dairy herd management practices and make recommendations for improvements; 2) visit local dairy farms and gain knowledge of different farms' management practices; 3) meet and interact with potential employers from the dairy industry during the contest; 4) evaluate herd records and utilize knowledge of dairy herd management software and computer presentation tools; 5) test their speaking, presentation, and problem-solving skills; and 6) work as a team to build consensus and tag-team speaking formats. Teams of four undergraduate students critically evaluate a commercial dairy farm using herd records, a description of farm operations, and tour of the farm facilities. The farmer answers questions pertaining to management of the farm in a group interview with all teams and in a separate interview with each individual team. Teams give a 20-min presentation that is scored on the description and assessment of the management practices and recommendations for improvements in management and facilities. Additionally, scoring is based on apparent level of preparation, speaking, presentation skills, and responses to judges' questions. The judges are university specialists and dairy industry professionals. This capstone experience allows students to interact with dairy farmers and representatives from the dairy industry and expands their knowledge and skills gained during their academic career.


Subject(s)
Agriculture/education , Dairying , Dairying/education , Interinstitutional Relations , Universities , Agriculture/organization & administration , Animals , Cattle , Dairying/methods , Dairying/organization & administration , Female , Michigan
13.
JAMA ; 286(19): 2437-40, 2001 Nov 21.
Article in English | MEDLINE | ID: mdl-11712939

ABSTRACT

CONTEXT: Oculopharyngeal muscular dystrophy (OPMD) is a rare myopathy caused by polyalanine triplet repeat expansion in the gene for poly(A) binding protein 2 (PABP2) and is found in isolated cohorts throughout the world. We have observed numerous cases of OPMD in New Mexico. OBJECTIVE: To characterize the clinical, genetic, and demographic features of the OPMD population in New Mexico. DESIGN, SETTING, AND PARTICIPANTS: Cohort study with analysis of outpatient clinic medical records from 1965 to 2001 at the University of New Mexico Hospital and the New Mexico VA Health Care System in Albuquerque, which serve the entire state. MAIN OUTCOME MEASURES: Clinical phenotype, supplemented with genetic confirmation (n = 10 patients) and in-depth clinical evaluations (n = 49 patients). RESULTS: We identified 216 cases of OPMD (99 women and 117 men) from 39 kindreds of New Mexicans spanning up to 4 generations. All patients were Hispanic, and the majority of probands came from northern New Mexico. In patients who had both ocular and pharyngeal muscle weakness, ptosis was just as likely to occur before or concurrent with dysphagia. Proximal limb muscle weakness and gait abnormalities were common and occurred later than ocular or pharyngeal weakness. The clinical expression of OPMD caused marked debility, although life-table analysis showed no decrease in life expectancy compared with unaffected family members (P =.81). Ten individuals from different kindreds were found to have an identical polyalanine triplet repeat expansion ([GCG](9)) in the PABP2 gene. CONCLUSIONS: Individuals in this cohort had clinical and genetic characteristics of classic OPMD. Longevity was not affected, but patients experienced considerable morbidity. The origin of the PABP2 mutation in New Mexican OPMD patients is unclear, although the geographic and genetic isolation of northern New Mexicans with a long ancestry in this region may have contributed to the development of this cohort. This disease cohort represents a large and previously unrecognized health care issue in the state of New Mexico and should serve to raise the awareness of this disorder among clinicians who treat Hispanics in the Southwest and throughout the United States.


Subject(s)
Hispanic or Latino/genetics , Muscular Dystrophies/ethnology , Adult , Aged , DNA-Binding Proteins/genetics , Female , Hispanic or Latino/statistics & numerical data , Humans , Life Tables , Male , Middle Aged , Muscular Dystrophies/diagnosis , Muscular Dystrophies/epidemiology , Muscular Dystrophies/genetics , New Mexico/epidemiology , Phenotype , Poly(A)-Binding Protein II , Trinucleotide Repeat Expansion
14.
J Neurol Sci ; 187(1-2): 61-7, 2001 Jun 15.
Article in English | MEDLINE | ID: mdl-11440746

ABSTRACT

To investigate the pathogenesis of influenza myositis in animals, juvenile BALB/c mice were inoculated with influenza B/Lee virus intramuscularly into the right quadriceps muscle. Chicken normal allantoic fluid (NAF) or phosphate-buffered saline (PBS) was injected into the left quadriceps of control mice and in some virus-infected mice. Serum creatinine phosphokinase (CPK) levels rose significantly on days 1 and 2 post-inoculation (PI) in only virus-inoculated mice. On days 2 and 3 PI, right quadriceps muscles developed scattered foci of a predominantly mononuclear inflammation in the perimysial connective tissue often adjacent to degenerating or necrotic muscle fibers. Immunofluorescent staining with specific anti-influenza B virus antisera showed muscle fibers that contained specific staining in nuclei and adjacent cytoplasm. Skip areas of staining within muscle fibers suggested that not all muscle nuclei within an individual muscle fiber were infected. A continuous fall in infectious virus titer in the right quadriceps muscles suggested the initial virus inoculum became inactivated and progeny virions were not produced. Left quadriceps muscle never had muscle necrosis or endomysial inflammation, specific staining of viral antigen, virus isolation, or viral RNA detected by the reverse transcriptase polymerase chain reaction assay. These findings support the hypothesis that a non-permissive influenza viral infection can develop in murine skeletal muscle that can damage specific nuclear domains of muscle fibers producing muscle degeneration or necrosis. A similar type of muscle infection may develop in humans that occasionally develop focal myositis during influenza.


Subject(s)
Influenza B virus/pathogenicity , Muscle, Skeletal/virology , Myositis/virology , Orthomyxoviridae Infections/complications , Animals , Creatine Kinase/blood , Fluorescent Antibody Technique , Influenza B virus/physiology , Mice , Mice, Inbred BALB C , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Myositis/pathology , Myositis/physiopathology , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/physiopathology , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Viral Load
15.
Clin Infect Dis ; 32(6): 979-82, 2001 Mar 15.
Article in English | MEDLINE | ID: mdl-11247722

ABSTRACT

A patient residing in New Mexico had murine typhus diagnosed. A novel molecular assay was performed at the Centers for Disease Control and Prevention, and Rickettsia prowazekii, the agent of epidemic typhus, was found, rather than R. typhi. To our knowledge, this is the first reported case of epidemic typhus confirmed by means of polymerase chain reaction--based testing of cerebrospinal fluid, and it introduces a novel assay for the molecular diagnosis of both epidemic and murine typhus.


Subject(s)
Meningitis, Bacterial/epidemiology , Rickettsia prowazekii/genetics , Typhus, Epidemic Louse-Borne/epidemiology , DNA, Bacterial/analysis , Humans , Male , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/diagnosis , Middle Aged , Polymerase Chain Reaction , Rickettsia prowazekii/isolation & purification , Southwestern United States/epidemiology , Typhus, Epidemic Louse-Borne/cerebrospinal fluid , Typhus, Epidemic Louse-Borne/diagnosis
16.
Ann Neurol ; 48(5): 812-5, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11079550

ABSTRACT

Intranuclear inclusions are one of the ultrastructural hallmarks of oculopharyngeal muscular dystrophy (OPMD), a disorder caused by small polyalanine (GCG) expansions in the gene that codes for a ubiquitous nuclear protein called poly(A) binding protein 2 (PABP2). We studied OPMD skeletal muscle and found that 1.0 to 10.0% of myocyte nuclei contained discreet PABP2 immunoreactive intranuclear inclusions, providing the first direct evidence of the relation between the proposed gene for OPMD and the pathology of OPMD.


Subject(s)
Inclusion Bodies/pathology , Muscles/pathology , Muscular Dystrophies/genetics , Muscular Dystrophies/pathology , RNA-Binding Proteins/analysis , Humans , Immunohistochemistry , Poly(A)-Binding Proteins
17.
J Neurovirol ; 6(6): 529-36, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11175325

ABSTRACT

To determine whether some constitutional symptoms of influenza, such as headache, myalgia and nausea, could represent a viral infection of brain, muscle, and liver, we inoculated juvenile Balb/c mice intranasally with 103 plaque forming units of influenza B/Lee virus. Blood, brain, liver, skeletal muscle, and lung tissues were removed aseptically and assayed for infectivity by a plaque assay, viral RNA by reverse transcriptase-polymerase chain reaction (RT - PCR), viral antigen by immunoperoxidase staining, and histologic changes by light microscopy. Mice became ill 2 - 3 days post inoculation (PI). A productive viral infection of the lungs developed from days 1 - 8 with maxima of virus titers, pneumonia, and the number of immunoperoxidase staining lung cells occurring on days 2 - 6 PI. Virus isolation from blood was rare and viral RNA was detected intermittently in blood by RT - PCR. In many animals, a non-permissive or abortive infection of brain occurred from days 1 - 8 and peaked on days 3 - 4 PI. Viral RNA was detected in brain tissue and viral antigen was seen in cerebral endothelial cells but infectious virus was rarely isolated from brain. In liver, viral RNA was detected and viral antigen was seen occasionally in hepatocytes. In skeletal muscle, viral RNA was detected but neither infectious virus nor viral antigen was seen. A correlation existed between the severity of the illness, pneumonia, lung virus titer, viral antigen in lung cells, and extent of a non-permissive viral infection of brain and liver but not muscle. These studies demonstrate that following intranasal infection of influenza virus in mice, a viral pneumonia develops with subsequent intermittent viremia and non-permissive or abortive infection of brain, liver and muscle.


Subject(s)
Brain/virology , Influenza B virus/physiology , Liver/virology , Muscle, Skeletal/virology , Orthomyxoviridae Infections/virology , Administration, Intranasal , Animals , Antigens, Viral/analysis , Hepatocytes/virology , Immunoenzyme Techniques , Influenza B virus/isolation & purification , Lung/virology , Mice , Mice, Inbred BALB C , Organ Specificity , Orthomyxoviridae Infections/pathology , Pneumonia, Viral/virology , RNA, Viral/analysis , Reverse Transcriptase Polymerase Chain Reaction , Viral Plaque Assay , Viremia/virology , Virus Replication
18.
Am J Vet Res ; 60(11): 1430-5, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10566822

ABSTRACT

OBJECTIVES: To evaluate the effects of halothane and isoflurane on cardiovascular function and serum total and ionized calcium concentrations in horses, and to determine whether administration of calcium gluconate would attenuate these effects. ANIMALS: 6 clinically normal adult Thoroughbreds. PROCEDURE: Catheters were inserted for measurement of arterial blood pressures, pulmonary arterial blood pressures, right ventricular pressure (for determination of myocardial contractility), right atrial pressure, and cardiac output and for collection of arterial blood samples. Anesthesia was then induced with xylazine hydrochloride and ketamine hydrochloride and maintained with halothane or isoflurane. An i.v. infusion of calcium gluconate was begun 75 minutes after anesthetic induction; dosage of calcium gluconate was 0.1 mg/kg of body weight/min for the first 15 minutes, 0.2 mg/kg/min for the next 15 minutes, and 0.4 mg/kg/min for an additional 15 minutes. Data were collected before, during, and after administration of calcium gluconate. RESULTS: Halothane and isoflurane decreased myocardial contractility, cardiac index, and mean arterial pressure, but halothane caused greater depression than isoflurane. Calcium gluconate attenuated the anesthetic-induced depression in cardiac index, stroke index, and maximal rate of increase in right ventricular pressure when horses were anesthetized with isoflurane. When horses were anesthetized with halothane, a higher dosage of calcium gluconate was required to attenuate the depression in stroke index and maximal rate of increase in right ventricular pressure; cardiac index was not changed with calcium administration. CONCLUSIONS AND CLINICAL RELEVANCE: I.v. administration of calcium gluconate may support myocardial function in horses anesthetized with isoflurane.


Subject(s)
Calcium/blood , Halothane/pharmacology , Hemodynamics/drug effects , Horses/physiology , Isoflurane/pharmacology , Anesthesia, Inhalation/veterinary , Animals , Blood Pressure/drug effects , Cardiac Output/drug effects , Female , Hemodynamics/physiology , Male , Orchiectomy , Pulmonary Artery/drug effects , Stroke Volume/drug effects , Time Factors
19.
Neurol Clin ; 17(4): 761-81, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10517927

ABSTRACT

This review discusses a practical approach to the patient with possible fungal infection of the central nervous system (CNS). Difficulties in establishing the diagnosis come from the nonspecific clinical syndromes (subacute meningitis, meningoencephalitis, and brain abscess) and the low isolation rate of fungi from cerebrospinal fluid (CSF). Helpful diagnostic clues often come from knowledge of the patient's geographic travels, risk factors, evidence of systemic organ infection, and fungal serologic tests. Standard and new antifungal agents are evaluated and the initial and suppressive drug management of the common fungal infections is presented.


Subject(s)
Central Nervous System Fungal Infections/diagnosis , Central Nervous System Fungal Infections/drug therapy , Central Nervous System Fungal Infections/microbiology , Humans , Risk Factors
20.
Am J Vet Res ; 60(7): 872-9, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10407482

ABSTRACT

OBJECTIVES: To determine the most repeatable method for evaluating right ventricular relaxation rate in horses and to determine and compare effects of isoflurane or halothane with and without the added influence of intravenously administered calcium gluconate on right ventricular relaxation rates in horses. ANIMALS: 6 Thoroughbred horses from 2 to 4 years old. PROCEDURE: 6 models (2 for monoexponential decay with zero asymptote, 3 for monoexponential decay with variable asymptote, and 1 for biexponential decay) for determining right ventricular relaxation rate were assessed in conscious and anesthetized horses. The 2 methods yielding the most repeatable results then were used to determine right ventricular relaxation rates in horses anesthetized with isoflurane or halothane before, during, and after i.v. administration of calcium gluconate. Right ventricular pressure was measured, using a catheter-tip high-fidelity pressure transducer, and results were digitized at 500 Hz from minimum rate of change in ventricular pressure. RESULTS: 2 models that used monoexponential decay with zero asymptote repeatedly produced an estimate for relaxation rate and were used to analyze effects of anesthesia and calcium gluconate administration on relaxation rate. Isoflurane and halothane each prolonged right ventricular relaxation rate, with greater prolongation evident in halothane-anesthetized horses. Calcium gluconate attenuated the anesthesia-induced prolongation in right ventricular relaxation rate, with greater response obtained in isoflurane-anesthetized horses. CONCLUSIONS AND CLINICAL RELEVANCE: Right ventricular relaxation rate in horses is assessed best by use of a monoexponential decay model with zero asymptote and nonlinear regression. Intravenous administration of calcium gluconate to isoflurane-anesthetized horses best preserves myocardial relaxant function.


Subject(s)
Anesthetics, Inhalation/therapeutic use , Heart Function Tests/veterinary , Heart Ventricles/physiopathology , Horse Diseases/physiopathology , Models, Biological , Animals , Calcium Gluconate/therapeutic use , Female , Halothane/therapeutic use , Horse Diseases/diagnosis , Horses , Injections, Intravenous/veterinary , Isoflurane/therapeutic use , Male , Regression Analysis , Reproducibility of Results , Xylazine/therapeutic use
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