Hypermetabolism or hyperglycolysis.
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Biomedical subjects
Publications and source records attributed to J Cruz.
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The revised French-American-British (FAB) classification system for acute myeloid leukemia (AML) recommends the determination of serum lysozyme (SL) or urine lysozyme (UL) levels as an aid in distinguishing acute myeloblastic leukemia with maturation (FAB M2) from acute myelomonocytic leukemia (M4). We reviewed retrospectively 208 cases of adult leukemia in which SL and/or UL were obtained. Elevated lysozyme levels were not found in any of the M0, M3, or M7 cases, but were increased (false positive) in three (14%) M1 cases, 18 (19%) M2 cases and one (20%) M6 case. Although a UL value in excess of 3x normal was found in most cases of AML M4 and M5, only five (11%) M4 cases and three (20%) M5 cases had SL elevations of this magnitude. Lysozyme levels need to be interpreted in conjunction with other parameters for FAB classification.
An isochromosome 12p [i(12p)], typical of germ cell tumours (GCT), has, to date, been observed in 10 cases of acute myeloid leukaemia (AML) or myelodysplastic syndrome, nine of which had concurrent or preceding GCT. We report two i(12p)-positive AML cases without clinical evidence of GCT. One patient with AML-M1 had two i(12p) as the only cytogenetic anomalies. In the other case of AML-M3 with t(15;17)(q22;q11-12) at diagnosis, the i(12p) was clearly a secondary rearrangement since it first appeared at relapse and always accompanied the t(15;17). Our results suggest that i(12p) does not always indicate neoplastic disease of germ cell origin.
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OBJECTIVE: To evaluate outcome from severe acute traumatic diffuse brain swelling, in relation to early patterns of global cerebral extraction of oxygen. DESIGN: Prospective, interventional study. SETTING: Neuroscience intensive care unit of a university hospital. PATIENTS: Adults (n = 205) with acute, essentially isolated brain trauma (predominantly diffuse brain swelling), undergoing routine early monitoring of cerebral extraction of oxygen and intracranial pressure, along with other monitoring modalities. INTERVENTIONS: Routine neuroemergency procedures. MEASUREMENTS AND MAIN RESULTS: Cerebral extraction of oxygen (arteriojugular oxyhemoglobin saturation difference) was measured in each patient, early in the acute phase (2 to 8 hrs postinjury). Outcome at 6 months postinjury was significantly better in patients with initially increased cerebral extraction of oxygen (>42%) than in those patients with normal (24% to 42%) or decreased (<24%) values. In contrast, no significant differences were found among these three groups with respect to age, initial Glasgow Coma Scale score, intracranial pressure, cerebral perfusion pressure, PaCO2, total hemoglobin content, and time from injury when the initial measurements were performed. CONCLUSIONS: Initially increased cerebral extraction of oxygen appears to indicate global cerebral viability rather than cerebral ischemia in patients with acute traumatic diffuse brain swelling.
Phenylketonuria (PKU) is caused by mutation(s) in the phenylalanine hydroxylase (PAH) gene which lead to deficient PAH activity and an accumulation of phenylalanine in the blood. The primary pathologic finding is hypomyelination and gliosis of central nervous system white matter. Similar white matter pathology is observed in the Pahenu2 mouse, a genetic model for PKU. We studied this mouse to examine the basis for these neuropathologic changes in PKU and to determine if hypomyelination and gliosis occur independently or are interrelated. Although white matter tracts within PKU brains are hypomyelinated, immunostaining and Western blot analyses revealed that these tracts contain abundant amounts of myelin markers, i.e. myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'phosphohydrolase, and myelin/oligodendrocyte-specific protein (MOSP). However, Western blot analyses also showed that MBP isoform expression was aberrant. Investigation of individual cells was performed by extraction of tissue sections with Triton X-100. Most of the MOSP was extracted, with the remaining MOSP clearly visible in dual labeled cells, i.e. MOSP was colocalized along glial fibrillary acidic protein (GFAP) filaments. Cells expressing both MBP and GFAP were also identified in optic tract. Double labeling with a riboprobe for MBP and antibodies specific for GFAP revealed that the majority of GFAP-positive cells expressed MBP mRNA. Our in vitro studies examined the response of cultured wild type oligodendrocytes to elevated phenylalanine for 4 weeks (wk). Under these conditions, about 50 these conditions, about 50% of the oligodendrocytes expressed GFAP filaments and failed to elaborate membrane sheets. Proliferation of astrocytes appears not to be the source of gliosis, since the nuclei of GFAP-positive cells in the PKU brains did not immunostain for proliferating cell nuclear antigen. Dual-labeled cells were detected in normal mouse brain sections; however, PKU mouse white matter tracts were found to contain about twice the number of dual-labeled cells compared to normal tissue. Taken together, these data suggest that both myelinating and nonmyelinating oligodendrocytes are present in the normal adult brain, and that in response to a toxic factor such as elevated phenylalanine, myelinating oligodendrocytes adopt a nonmyelinating phenotype that expresses GFAP. Since myelinating Schwann cells and GFAP-positive nonmyelinating Schwann cells are normally present in adult peripheral nerve, and the myelinating Schwann cells react to pathologic situations by switching to GFAP-positive nonmyelinating cells, it may be that oligodendrocytes and Schwann cells are more similar than previously thought.
A case of gunshot wound to the head is presented, in which the patient made a satisfactory recovery after a prolonged period of elevated intracranial pressure and increased cerebral extraction of oxygen. Even though cerebral extraction of oxygen was increased in the most acute phase, the arteriojugular lactate difference was never abnormally decreased (ischemic). This finding indicated that, in this patient, increased cerebral extraction of oxygen was not sufficient to result in global cerebral ischemia (increased cerebral lactate production). To our knowledge, this is the first report on frequent serial assessment of cerebral extraction of oxygen and lactate production in severe penetrating head injury.
Verification of specimens positive for Chlamydia trachomatis by enzyme immunoassay (EIA) has been recommended when testing low prevalence populations. This study compared direct fluorescent antibody (DFA) and blocking antibody (BLA) verification assays in specimens presumptively positive for C. trachomatis by the Syva Microtrak II EIA. Of 1785 specimens originally tested by EIA, 96 were presumptively positive for C. trachomatis. Verification assays were concordant in 86 specimens (69 positive, 17 negative); nine of the remaining samples gave positive results in a second EIA and one was unresolved. Both verification assays gave some false-negative results. When initial EIA absorbance values were correlated with verified results, all EIA false positive results had absorbances in the low range (less than a three-fold increase over assay cut-off values). Verification of EIA results by both DFA and BLA was effective in detecting false positive results, but confining verification to low-value positive specimens could be considered for cost effective C. trachomatis testing.
OBJECTIVE: To develop a resource, consisting of comprehensive data and lymphoblastoid cell lines, of well-characterized NIDDM families that will be available to the scientific community for genetic studies of NIDDM. RESEARCH DESIGN AND METHODS: Non-Hispanic white, Hispanic, African-American, and Japanese-American multiplex NIDDM families, with a minimum of one affected sib-pair, are being collected by the eight Harold Rifkin Family Acquisition Centers. Detailed family and medical histories are obtained from all participants. Family members with diabetes have fasting blood samples drawn, while nondiabetic family members have an oral glucose tolerance test and, when possible, insulin sensitivity and insulin secretion measurements by frequently sampled intravenous glucose tolerance testing or euglycemic insulin clamp. Lymphoblastoid cell lines are established for all participants. RESULTS: Over 1,400 individuals from approximately 220 families have been studied since the start of the GENNID (Genetics of NIDDM) program in July 1993. The goal is that by July 1997, data from 300 non-Hispanic white families, > 100 Hispanic families, > 100 African-American families, and 15 Japanese-American families will have been collected. CONCLUSIONS: The identification of the genes responsible for NIDDM may now be achievable, but only if sound phenotypic data are linked to genetic material from a large number of well-described multiplex families. The GENNID project of the American Diabetes Association is creating a comprehensive resource that will expedite the identification of the genetic basis of NIDDM.
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Global cerebrovenous oxygenation was evaluated before and after intravenous administration of pentobarbital sodium for the management of refractory intracranial hypertension in 151 comatose patients who had acute traumatic brain swelling. Two groups of patients were identified: a group in which the jugular oxyhemoglobin saturation (SjO2) remained at or above 45% after pentobarbital bolus, and a group in which the SjO2 dropped below 45%. The two groups were matched by predominant findings on computerized tomography scans of the head, as well as age, postresuscitation Glasgow Coma Scale scores, levels of total hemoglobin content, SjO2, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) prior to pentobarbital bolus. Outcomes were significantly worse (p < 0.0001) in patients who developed decreases in SjO2 to levels below 45% than in those whose SjO2 remained at or above 45%, despite the fact that there were no significant differences between the two groups with regard to ICP and CPP after an intravenous bolus of pentobarbital.
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Acquired haemophilia is a rare disorder that it is associated with several diseases. Patients may present with spontaneous haematomas in different places which can sometimes be fatal. We present a 69-year-old woman with breast carcinoma who developed a factor VIII inhibitor. The initial haemorrhagic event was a spontaneous deep muscular haematoma in the right leg mimicking a deep venous thrombosis. She was successfully treated with prednisone.
OBJECTIVE: To evaluate a novel parameter of global cerebral oxygen metabolism, the estimated cerebral metabolic rate of oxygen, for its clinical utility in monitoring acute, severely brain-injured patients. DESIGN: Prospective, observational study. SETTING: Neuroscience intensive care unit of a university hospital. PATIENTS: Sixty-six adults with acute brain trauma undergoing 133Xe regional cerebral blood flow and global cerebral oxygen metabolic studies, in conjunction with other routine monitoring techniques. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Estimated cerebral metabolic rate of oxygen was calculated as the product of PaCO2 and arterio-jugular oxygen content difference, and compared with the measured cerebral metabolic rate of oxygen (the product of mean regional cerebral blood flow and arterio-jugular oxygen content difference). Good correlations were found between the estimated and the true values (r2 = .56/.67, p < .0001) in 91 studies performed in 66 patients. CONCLUSIONS: These findings suggest that the estimated cerebral metabolic rate of oxygen is a useful substitute for the traditional cerebral metabolic rate of oxygen when cerebral blood flow information is not available. In addition, with this parameter, the patient's metabolic status can be assessed more frequently than with cerebral blood flow studies. These measurements do not require special instrumentation and can be done in any intensive care setting.
OBJECTIVES: To evaluate normal or high cerebral perfusion pressure in relation to cerebral blood flow and oxygen metabolism, as well as other multivariate cerebral hemodynamic and metabolic interrelationships, in acute brain trauma in humans. DESIGN: Prospective, observational study. SETTING: Neuroscience intensive care unit of a university hospital. PATIENTS: Adults (n = 66) with severe acute brain trauma (Glasgow Coma Scale scores from 4 to 8), undergoing multivariate physiologic studies involving cerebral perfusion pressure, cerebral blood flow, cerebral metabolic rate of oxygen consumption, total hemoglobin content, arterio-jugular oxygen content difference, and cerebral vascular resistance, along with other routine procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Statistical analysis did not demonstrate any correlation between cerebral perfusion pressure and cerebral blood flow, between cerebral perfusion pressure and arterio-jugular oxygen content difference, and between cerebral perfusion pressure and cerebral metabolic rate of oxygen consumption, over a broad spectrum of perfusion pressures ranging from 60 to 130 mm Hg. In contrast, a significant negative correlation was found between cerebral vascular resistance and cerebral blood flow, where higher values of cerebral vascular resistance were associated with lower blood flow levels, and vice versa. CONCLUSIONS: In severe acute brain trauma, cerebral hemodynamic and oxygen metabolic variables are not necessarily correlated with normal or even high levels of cerebral perfusion pressure. Under these circumstances, cerebral vascular resistance (not perfusion pressure) is more closely correlated with different patterns of cerebral blood flow and metabolism.