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Biomedical subjects

C J Eskey

Publications and source records attributed to C J Eskey.

13 recordsLinked to original sources

Two cases of rapid onset Parkinson's syndrome following toxic ingestion of ethylene glycol and methanol.

Ethylene glycol and methanol are toxic alcohols commonly found in a variety of commercial products. We report two cases, one associated with ethylene glycol and one with methanol poisoning, which both led to acute hemorrhagic necrosis of the basal ganglia and resulted in acute Parkinson's syndrome. It is unlikely that oxalate crystal deposition is the only mechanism for such basal ganglia necrosis, because similar findings were seen following methanol intoxication. We discuss other possible mechanisms that may contribute towards this unusual neurotoxicity. Both of our patients survived their toxic ingestions, but then developed acute Parkinson's syndrome within 10 days of the ingestion. However, the patient who ingested methanol developed respiratory muscle stiffness/weakness, which responded poorly to anti-Parkinsonian drug therapy. Treatment with carbidopa/levodopa improved cogwheel rigidity and bradykinesia in both patients. We conclude that acute Parkinsonism is one of the lesser-recognized devastating complications of both ethylene glycol and methanol poisoning.

Acute Disease↗

Focal paraneoplastic limbic encephalitis presenting as orgasmic epilepsy.

PURPOSE: To report orgasmic epilepsy as a manifestation of paraneoplastic limbic encephalitis in a patient with small cell lung cancer. CASE REPORT: A 57 years-old woman presented with 2 month history of daily spells that consisted of a sudden pleasure provoking feeling described 'like an orgasm' lasting for 30 s to 1 min. She was a heavy smoker and had noted recent weight loss. Bronchial biopsy, following the finding of a right lung mass, confirmed the diagnosis of small cell lung cancer (SCLC). Spells subsided after starting carbamazepine. The lung cancer was treated with chemotherapy and chest radiation therapy resulting in a complete radiologic response. RESULTS: Brain magnetic resonance imaging (MRI) revealed left temporal lobe area of increased signal on T2 and FLAIR sequence. T1-weighted images after contrast administration demonstrated a circumscribed area of enhancement in the left anterior medial temporal lobe. Electroencephalogram (EEG) showed focal left mid-temporal sharp waves and intermittent slowing. Anti-Hu antibodies were detected in her serum supporting a diagnosis of paraneoplastic limbic encephalitis as the cause of her orgasmic epilepsy. The patient has been followed for 2 years after treatment without tumor recurrence or neurological deterioration. CONCLUSION: Orgasmic epilepsy is another mode of presentation of paraneoplastic limbic encephalitis leading to the diagnosis of an occult SCLC. EEG and MRI findings suggest that in this case the seizures originated from the left hemisphere. It is possible that early recognition and treatment of the SCLC will improve the prognosis of this neurologic entity.

Antineoplastic Combined Chemotherapy Protocols↗

Fluoroscopy-guided lumbar puncture: decreased frequency of traumatic tap and implications for the assessment of CT-negative acute subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: In patients with suspected subarachnoid hemorrhage (SAH) and negative CT findings, the iatrogenic introduction of RBCs into the CSF during lumbar puncture may lead to a misdiagnosis. We tested the hypothesis that the risk of traumatic lumbar puncture is lower with the fluoroscopy-guided technique than with the standard bedside technique. METHODS: Data were collected retrospectively from two populations: adult inpatients undergoing standard bedside lumbar puncture for any reason and adult patients undergoing fluoroscopy-guided lumbar puncture for myelography. Patients with SAH and CSF samples with significant abnormalities other than erythrocytosis (ie, CSF leukocytosis, xanthochromia, or elevated protein) were excluded. In all, 1489 bedside procedures and 723 fluoroscopy-guided procedures met the criteria. RESULTS: We found a significant difference in the level of iatrogenic CSF erythrocytosis produced by the two procedures. Using a cutoff of 1000 cells/mm(3), the frequency of traumatic lumbar puncture was 10.1% for bedside lumbar puncture and 3.5% for fluoroscopy-guided lumbar puncture. With fluoroscopic guidance, the frequency of a traumatic tap varied significantly with the operator, ranging from 0% to 24%. CONCLUSION: The use of fluoroscopy-guided lumbar puncture in patients with suspected SAH and negative CT findings should reduce the frequency of false-positive diagnoses of acute SAH as well as the number of unnecessary angiograms for patients with suspected SAH but no underlying intracranial vascular malformation.

Fluoroscopy↗

Imaging of benign and malignant soft tissue tumors of the neck.

Soft tissue tumors of the neck are a heterogeneous group of neoplasms arising from adipose, muscular, and fibrous tissue. With the exception of lymphomas, they account for only a small fraction of neck masses. Nevertheless, accurate diagnosis is important since the behavior of these neoplasms differs markedly from each other and from other head and neck masses. Noninvasive imaging, usually with CT and MR imaging, plays an important role in diagnostic evaluation and treatment planning for these tumors. In some cases, imaging features may be suggestive of a single entity. In most cases, imaging is needed to assess the location and extent of the tumor prior to biopsy or excision. This article discusses imaging techniques used for such assessment, the imaging features that help to separate these neoplasms from other head and neck tumors, and the behavior and imaging features of each of the more common benign and malignant soft tissue tumors that occur in the neck.

Diagnostic Imaging↗

Intraluminal colon pressure dynamics with Valsalva maneuver during air enema study.

PURPOSE: To determine the effects of the Valsalva maneuver on intraluminal colon pressure during air enema studies. MATERIALS AND METHODS: Air enema studies were performed in four adult volunteers, and intraluminal colon pressure measurements were recorded with a high-speed electronic strip chart and aneroid gauge methods. One hundred thirty-five Valsalva maneuvers were produced with open- and closed-glottis maneuvers, with varying degrees of straining, and during normal peristalsis. RESULTS: Valsalva pressure waves are discrete waveforms that can be distinguished from baseline insufflation and normal peristaltic waves. Valsalva waves are of both simple and complex types. The range of peak Valsalva pressures was 12-148 mm Hg. Average mild, moderate, and vigorous pressures with a closed glottis were 22, 38, and 90 mm Hg, respectively. High pressures (120-130 mm Hg) were observed with open- and closed-glottis maneuvers. CONCLUSION: Valsalva maneuvers increase intracolonic pressure 12-148 mm Hg above baseline pressure. Valsalva pressure waves are discrete and can be accurately detected with both aneroid and electronic transducer systems.

Adult↗

Residence time distributions of various tracers in tumors: implications for drug delivery and blood flow measurement.

BACKGROUND: The evaluation of rates of tumor blood flow with small, rapidly diffusing tracers requires an accurate model for mass transport within the tissue and tracer biodistribution. It is generally assumed that the whole tumor or several tumor regions act as well-mixed compartments, an assumption that has never been evaluated in tumors. PURPOSE: The purpose of this study was to assess the accuracy of compartmental flow models in tissue-isolated tumors. METHODS: We measured the residence time distributions of various tracers with the use of ex vivo perfusion of tissue-isolated rat R3230AC mammary tumors. This approach permits simultaneous, independent measurements of total blood flow and tracer concentrations in afferent and efferent vessels. The isolated tumors were perfused with Krebs-Henseleit solution, to which could be added D2O saline and either 3% by volume F44-E (a perfluorocarbon emulsion) or 1% by weight fluorescein isothiocyanate (FITC)-albumin. A pulse of D2O and one of the other tracers was added to the perfusing liquid, and the relative concentrations of both D2O and perfluorocarbon or FITC-albumin were measured in the tumor effluent. D2O and the perfluorocarbon were measured with an imaging spectrometer tuned to either 2H or 19F. FITC-albumin concentrations were measured by luminescence spectrometry. The results were analyzed using various compartmental models. RESULTS: The tracer residence time distribution deviated from that expected for a single well-mixed compartment. Only half of the D2O left the tumor with a time constant consistent with the known perfusate flow. The remainder exited the tumor more rapidly than expected, and neither vascular shunting nor macroscopic flow heterogeneity accounts for this component of the D2O flow. However, two-compartment models provide an improved fit to the data. CONCLUSIONS: Our experiments demonstrate that the simple compartmental model used to estimate blood flow with diffusible tracers is not accurate. IMPLICATIONS: The nonideal blood flow found in our experiments reflects phenomena that may have important effects in the development of pharmacokinetic models of drug delivery to tumors. The accuracy of blood flow measurements, made with such techniques as nuclear magnetic resonance, positron-emission tomography, and computed tomography, may also be affected when they rely on the assumption that the tumor is a collection of well-mixed compartments.

Adenocarcinoma↗

A carbon-13 nuclear magnetic resonance investigation of the metabolic fluxes associated with glucose metabolism in human erythrocytes.

We have used [2-13C]D-glucose and carbon-13 nuclear magnetic resonance (NMR) spectroscopy to investigate metabolic fluxes through the major pathways of glucose metabolism in intact human erythrocytes and to determine the interactions among these pathways under conditions that perturb metabolism. Using the method described, we have been able to measure fluxes through the pentose phosphate pathway, phosphofructokinase, the 2,3-diphosphoglycerate bypass, and phosphoglycerate kinase, as well as glucose uptake, concurrently and in a single experiment. We have measured these fluxes in normal human erythrocytes under the following conditions: (1) fully oxygenated; (2) treated with methylene blue; and (3) deoxygenated. This method makes it possible to monitor various metabolic effects of stresses in normal and pathological states. Not only has 13C-NMR spectroscopy proved to be a useful method for measuring in vivo flux through the pentose phosphate pathway, but it has also provided additional information about the cycling of metabolites through the non-oxidative portion of the pentose phosphate pathway. Our evidence from experiments with [1-13C]-, [2-13C]-, and [3-13C]D-glucoses indicates that there is an observable reverse flux of fructose 6-phosphate through the reactions catalyzed by transketolase and transaldolase, even in the presence of a net flux through the pentose phosphate pathway.

Adult↗

Role of oxygen vs. glucose in energy metabolism in a mammary carcinoma perfused ex vivo: direct measurement by 31P NMR.

The role of glycolysis vs. respiration in tumor energy metabolism has been studied, to date, primarily in vitro by using single cells, multicellular spheroids, or tissue slices. With the advent of in vivo NMR spectroscopy, several investigators have shown that tumor energy status depends on its blood flow. Since manipulation of blood flow alters both oxygen and glucose delivery to a solid tumor, these studies have not been able to separate the relative contribution of oxygen vs. glucose in energy metabolism in vivo. In the present study, we have overcome this problem by combining two methods: the tissue-isolated R3230AC mammary adenocarcinoma perfused ex vivo and 31P NMR spectroscopy. The isolated tumor permits one to control the perfusion pressure as well as the metabolite concentrations in the perfusate. NMR spectroscopy permits one to measure the ratio of nucleoside triphosphate to inorganic phosphate (NTP/Pi) and pH. Our results show that (i) the NTP/Pi ratio ex vivo is similar to that observed in vivo prior to surgery, (ii) the NTP/Pi ratio is insensitive to flow changes at high flow rates but is proportional to flow rate at flows comparable to those found in vivo, (iii) the NTP/Pi ratio of these tumors is resistant to hypoxia and is not maintained when glucose is removed or replaced with glutamine, and (iv) although both O2 and glucose are consumed by these tumors, the effect of perfusate flow rate appears to be mediated largely through glucose delivery. The current approach not only provides information about the role of glycolysis vs. respiration in a rodent tumor but also is general and versatile enough to provide similar data in human tumors perfused ex vivo.

Adenocarcinoma↗

2H-nuclear magnetic resonance imaging of tumor blood flow: spatial and temporal heterogeneity in a tissue-isolated mammary adenocarcinoma.

2H-Nuclear magnetic resonance imaging of deuteron accumulation in tissue following an i.v. bolus of deuterium oxide provides a noninvasive means of constructing maps of tissue perfusion. With a measured arterial input function and a simple model for tissue-capillary exchange, these data can provide quantitative estimates of local flow. This technique was tested in rat brain and then applied to the study of spatial heterogeneity and temporal variation of blood flow in the tissue-isolated R3230AC mammary adenocarcinoma. Global flow from the brain averaged 0.96 ml/min.g, in good agreement with results obtained from other methods; the perfusion of brain was relatively homogeneous. Global tumor blood flow averaged 0.32 ml/min.g, ranging from 0.11 to 0.96 ml/min.g. Imaging revealed variations in perfusion both within and between the tumors that far exceeded those expected from brain flow heterogeneity and uncertainty in the flow estimates. By obtaining repeated flow images at 30-min intervals, it was possible to show that the regional blood flow shifted with time in single pixels and in multipixel regions. These experiments show that 2H-nuclear magnetic resonance may be useful in obtaining noninvasive and quantitative measurement of temporal blood flow changes in a solid tumor in vivo.

Adenocarcinoma↗

Measurement of cerebral blood flow in rat brain by 19F-NMR detection of trifluoromethane washout.

The washout of trifluoromethane (CHF3) from rat cerebral cortex was monitored by 19F NMR. After 15 min of inhalation of 67% CHF3/33% O2 the fluorine signal detected was in a steady state. The CHF3 was switched off rapidly at the endotracheal tube and the washout detected with 12-s time resolution. Two models were used to extract flow information, a simple exponential fit and a model which accounts for arterial CHF3 recirculation. In both cases, a two-compartment model fit the data significantly better than a one-compartment model. In both models, the faster time component varied with increasing pCO2, but no significant change in the slow component was detected. At control values of pCO2, there was a small difference in washout rate constants derived from the two models. At high pCO2, when tissue washout was comparable to arterial washout of CHF3, the model which accounted for arterial recirculation gave higher flows. Using this two-compartment model with correction for recirculation, a control flow (pCO2 = 35 mm Hg) of 0.73 +/- 0.04 ml/min/g was measured. Increasing plasma pCO2 increased the apparent flow six- to sevenfold with a 4.4% increase in flow per millimeter of Hg change in CO2. These results are qualitatively in agreement with results found by others using the washout of 133Xe. However, this method yields values for flow that are lower than those obtained using 133Xe washout, probably because of diffusion limitations of CHF3.

Animals↗