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Biomedical subjects

B Eisenberg

Publications and source records attributed to B Eisenberg.

At least 19 recordsLinked to original sources

Brain SPECT imaging and neuropsychological testing in coronary artery bypass patients: single photon emission computed tomography.

BACKGROUND: Cognitive deficits appear frequently after cardiac operation. While the etiology remains unclear, alterations in cerebral perfusion during cardiopulmonary bypass may be causative. Single photon emission computed tomography (SPECT) scanning utilizes a radiopharmaceutical to provide images of cerebral perfusion. We proposed to study the cerebral circulation of patients during coronary artery bypass operation employing cardiopulmonary bypass. METHODS: Thirty-five neurologically normal patients underwent preoperative SPECT brain scanning and neuropsychological testing. A second SPECT brain perfusion scan was obtained by administering the radioisotope during cardiopulmonary bypass, with subsequent scanning upon completion of the procedure. Postoperative neuropsychological testing was performed prior to discharge. RESULTS: Fourteen (40%) of patients demonstrated significant neuropsychological decline. Patients who suffered cognitive impairment were no different in demographic, general health, or surgical variables. Patients who demonstrated neuropsychological decline had significantly poorer cerebral perfusion both at baseline and during operation. CONCLUSIONS: Impaired cerebral perfusion at baseline may identify patients at risk for cognitive injury after cardiac operation. Alterations in cerebral perfusion during cardiopulmonary bypass is common, and may be a factor in neuropsychological deficits seen after cardiac operation.

Aged

Selectivity and permeation in calcium release channel of cardiac muscle: alkali metal ions.

Current was measured from single open channels of the calcium release channel (CRC) of cardiac sarcoplasmic reticulum (over the range +/-180 mV) in pure and mixed solutions (e.g., biionic conditions) of the alkali metal ions Li+, K+, Na+, Rb+, Cs+, ranging in concentration from 25 mM to 2 M. The current-voltage (I-V) relations were analyzed by an extension of the Poisson-Nernst-Planck (PNP) formulation of electrodiffusion, which includes local chemical interaction described by an offset in chemical potential, which likely reflects the difference in dehydration/solvation/rehydration energies in the entry/exit steps of permeation. The theory fits all of the data with few adjustable parameters: the diffusion coefficient of each ion species, the average effective charge distribution on the wall of the pore, and an offset in chemical potential for lithium and sodium ions. In particular, the theory explains the discrepancy between "selectivities" defined by conductance sequence and "selectivities" determined by the permeability ratios (i.e., reversal potentials) in biionic conditions. The extended PNP formulation seems to offer a successful combined treatment of selectivity and permeation. Conductance selectivity in this channel arises mostly from friction: different species of ions have different diffusion coefficients in the channel. Permeability selectivity of an ion is determined by its electrochemical potential gradient and local chemical interaction with the channel. Neither selectivity (in CRC) seems to involve different electrostatic interaction of different ions with the channel protein, even though the ions have widely varying diameters.

Animals

Local excision and chemoradiation for low rectal T1 and T2 cancers is an effective treatment.

Lesions located in the distal third of the rectum are usually treated with abdominoperineal resection or a low anterior resection with a coloanal anastomosis. However, in a select group of patients with favorable histology and a low probability of lymphatic spread, sphincter-sparing procedures will afford long-term disease-free survival and cure without the need for extensive, complicated surgery. We performed a 10-year retrospective review, including pathologic examination of specimens by a single pathologist, in an attempt to identify factors associated with a decreased disease-free survival. Thirty-five patients (median age, 71 years; range, 48-88) with low rectal carcinomas were treated with full-thickness disc excision (with or without chemoradiation), with curative intent. Median follow-up was 46 months (range, 8-120). There were 15 T1, 16 T2, and 4 T3 lesions. Tumors with poor histologic factors or greater than T1 received adjuvant radiation (with or without 5-fluorouracil). Four patients developed a local failure at a median of 21.5 months (range, 9-30) and were salvaged with abdominoperineal resection. The 5-year cancer-specific survival was 91 per cent. Negative margins approached statistical significance (P < 0.07) in influencing local control. We conclude that, when combined with chemoradiation for lesions deeper than submucosa or with adverse histologic factors, local resection of rectal cancer is an effective treatment in selected patients.

Aged

Ion permeation and glutamate residues linked by Poisson-Nernst-Planck theory in L-type calcium channels.

L-type Ca channels contain a cluster of four charged glutamate residues (EEEE locus), which seem essential for high Ca specificity. To understand how this highly charged structure might produce the currents and selectivity observed in this channel, a theory is needed that relates charge to current. We use an extended Poisson-Nernst-Planck (PNP2) theory to compute (mean) Coulombic interactions and thus to examine the role of the mean field electrostatic interactions in producing current and selectivity. The pore was modeled as a central cylinder with tapered atria; the cylinder (i.e., "pore proper") contained a uniform volume density of fixed charge equivalent to that of one to four carboxyl groups. The pore proper was assigned ion-specific, but spatially uniform, diffusion coefficients and excess chemical potentials. Thus electrostatic selection by valency was computed self-consistently, and selection by other features was also allowed. The five external parameters needed for a system of four ionic species (Na, Ca, Cl, and H) were determined analytically from published measurements of thre limiting conductances and two critical ion concentrations, while treating the pore as a macroscopic ion-exchange system in equilibrium with a uniform bath solution. The extended PNP equations were solved with these parameters, and the predictions were compared to currents measured in a variety of solutions over a range of transmembrane voltages. The extended PNP theory accurately predicted current-voltage relations, anomalous mole fraction effects in the observed current, saturation effects of varied Ca and Na concentrations, and block by protons. Pore geometry, dielectric permittivity, and the number of carboxyl groups had only weak effects. The successful prediction of Ca fluxes in this paper demonstrates that ad hoc electrostatic parameters, multiple discrete binding sites, and logistic assumptions of single-file movement are all unnecessary for the prediction of permeation in Ca channels over a wide range of conditions. Further work is needed, however, to understand the atomic origin of the fixed charge, excess chemical potentials, and diffusion coefficients of the channel. The Appendix uses PNP2 theory to predict ionic currents for published "barrier-and-well" energy profiles of this channel.

Biophysical Phenomena

Anomalous mole fraction effect, electrostatics, and binding in ionic channels.

Ionic channels bathed in mixed solutions of two permeant electrolytes often conduct less current than channels bathed in pure solutions of either. For many years, this anomalous mole fraction effect (AMFE) has been thought to occur only in single-file pores containing two or more ions at a time. Most thinking about channels incorporates this view. We show here that the AMFE arises naturally, as an electrostatic consequence of localized ion specific binding, if the average current through a channel is described by a theory (Poisson-Nernst-Planck, PNP) that computes the average electric field from the average concentration of charges in and near the channel. The theory contains only those ion-ion interactions mediated by the mean field, and it does not enforce single filing. The AMFE is predicted by PNP over a wide range of mean concentrations of ions in the channel; for example, it is predicted when (on the average) less, or much less, than one ion is found in the channel's pore. In this treatment, the AMFE arises, in large measure, from a depletion layer produced near a region of ion-specific binding. The small excess concentration of ions in the binding region repels all nearby ions of like charge, thereby creating a depletion layer. The overall conductance of the channel arises in effect from resistors in series, one from the binding region, one from the depletion zone, and one from the unbinding region. The highest value resistor (which occurs in the depletion zone) limits the overall series conductance. Here the AMFE is not the result of single filing or multiple occupancy, and so previous views of permeation need to be revised: the presence of an AMFE does not imply that ions permeate single file through a multiply occupied pore.

Binding Sites

Efficacy of selective unilateral exploration in hyperparathyroidism based on localization tests.

OBJECTIVES: To determine the success of unilateral exploration vs bilateral exploration for primary hyperparathyroidism and to analyze the validity of preoperative localization tests. DESIGN: Case-control study of patients who underwent surgical exploration (unilateral, n = 43; bilateral, n = 57) by 1 surgeon from January 1991 through May 1996 and who had ultrasound examination of the neck and thallium-technetium scintigraphy performed before parathyroid surgery. Initially, unilateral exploration was used sparingly, but it became the standard approach in 1994 if localization was correct. SETTING: Urban multispecialty clinic, teaching hospital. PATIENTS: One hundred consecutive patients who underwent surgical exploration for primary hyperparathyroidism. INTERVENTIONS: Ultrasonography of the neck, thallium-technetium scintigraphy, and parathyroidectomy. MAIN OUTCOME MEASURES: Imaging success, operative success, and operative time. RESULTS: In 94 patients with solitary adenomas, the adenoma was demonstrated by ultrasound scans in 66%, by thallium-technetium scintigraphy in 83%, and by either test in 87%. Correct identification by ultrasonography was 59%; by thallium-technetium scintigraphy, 75%; and together, 73%. Of 6 patients with multiple-gland disease, 2 were correctly identified by localization tests and 9 of 15 abnormal glands were demonstrated. Of the 43 unilateral explorations, 43 single adenomas and no cases of multiple-gland disease were identified; of the 57 bilateral explorations, 51 single adenomas and 6 cases of multiple-gland disease were identified. No complications occurred in either group. Hypercalcemia persisted in 3 patients who underwent bilateral exploration and recurrent hypercalcemia developed in 1 patient in each group. The average operative time for the unilateral procedure was 105 minutes, and for the bilateral procedure, 184 minutes (P < .001). Since 1994, 31 (66%) of 47 patients have had unilateral exploration based on correct localization tests. CONCLUSIONS: Unilateral exploration that is based on the results of localization tests requires less operative time and produces results similar to bilateral exploration.

Adenoma

Permeation through the calcium release channel of cardiac muscle.

Current voltage (I-V) relations were measured from the calcium release channel (CRC) of the sarcoplasmic reticulum of cardiac muscle in 12 KCl solutions, symmetrical and asymmetrical, from 25 mM to 2 M. I-V curves are nearly linear, in the voltage range +/- 150 mV approximately 12kT/e, even in asymmetrical solutions, e.g., 2 M // 100 mM. It is awkward to describe straight lines as sums of exponentials in a wide range of solutions and potentials, and so traditional barrier models have difficulty fitting this data. Diffusion theories with constant fields predict curvilinear I-V relations, and so they are also unsatisfactory. The Poisson and Nernst-Planck equations (PNP) form a diffusion theory with variable fields. They fit the data by using adjustable parameters for the diffusion constant of each ion and for the effective density of fixed (i.e., permanent) charge P(x) along the channel's "filter" (7-A diameter, 10 A long). If P(x) is described by just one parameter, independent of x (i.e., P(x) = P0 = -4.2 M), the fits are satisfactory (RMS error/RMS current = 6.4/67), and the estimates of diffusion coefficients are reasonable D(K) = 1.3 x 10(-6) cm2/s, D(Cl) = 3.9 x 10(-6) cm2/s. The CRC seems to have a small selectivity filter with a very high density of permanent charge. This may be a design principle of channels specialized for large flux. The Appendix derives barrier models, and their prefactor, from diffusion theories (with variable fields) and argues that barrier models are poor descriptions of CRCs in particular and open channels in general.

Calcium

Permeation through an open channel: Poisson-Nernst-Planck theory of a synthetic ionic channel.

The synthetic channel [acetyl-(LeuSerSerLeuLeuSerLeu)3-CONH2]6 (pore diameter approximately 8 A, length approximately 30 A) is a bundle of six alpha-helices with blocked termini. This simple channel has complex properties, which are difficult to explain, even qualitatively, by traditional theories: its single-channel currents rectify in symmetrical solutions and its selectivity (defined by reversal potential) is a sensitive function of bathing solution. These complex properties can be fit quantitatively if the channel has fixed charge at its ends, forming a kind of macrodipole, bracketing a central charged region, and the shielding of the fixed charges is described by the Poisson-Nernst-Planck (PNP) equations. PNP fits current voltage relations measured in 15 solutions with an r.m.s. error of 3.6% using four adjustable parameters: the diffusion coefficients in the channel's pore DK = 2.1 x 10(-6) and DCl = 2.6 x 10(-7) cm2/s; and the fixed charge at the ends of the channel of +/- 0.12e (with unequal densities 0.71 M = 0.021e/A on the N-side and -1.9 M = -0.058e/A on the C-side). The fixed charge in the central region is 0.31e (with density P2 = 0.47 M = 0.014e/A). In contrast to traditional theories, PNP computes the electric field in the open channel from all of the charges in the system, by a rapid and accurate numerical procedure. In essence, PNP is a theory of the shielding of fixed (i.e., permanent) charge of the channel by mobile charge and by the ionic atmosphere in and near the channel's pore. The theory fits a wide range of data because the ionic contents and potential profile in the channel change significantly with experimental conditions, as they must, if the channel simultaneously satisfies the Poisson and Nernst-Planck equations and boundary conditions. Qualitatively speaking, the theory shows that small changes in the ionic atmosphere of the channel (i.e., shielding) make big changes in the potential profile and even bigger changes in flux, because potential is a sensitive function of charge and shielding, and flux is an exponential function of potential.

Computer Simulation

Customer service in health care: a new era.

Intensified competition in healthcare is stimulating an enhanced focus on consumer satisfaction. Critical barriers to customer service are being dismantled and hospitals are instituting comprehensive models to promote consumer-oriented environments.

Communication

Parathyroid scintigraphy.

Scintigraphy of the parathyroid glands continues to be controversial from several standpoints, including radiopharmaceutical choice, imaging protocol, results, and utility in clinical situations. This article reviews: the anatomy, physiology and pathology of the parathyroid glands; mechanisms of radiopharmaceutical localization; commonly accepted imaging protocols; image results; and the appropriate use of parathyroid scintigraphy.

Humans

Role of LFA-3, ICAM-1, and MHC class I on the sensitivity of human tumor cells to LAK cells.

Cellular adhesion molecules have been shown to be involved in tumor cell killing by cytotoxic cells such as natural killer (NK), lymphokine-activated killer (LAK), and T cells, but the precise mechanisms involved have not been clearly determined and a single target molecule has not been identified. We have examined the relative sensitivities of a panel of human tumor cell lines to LAK cell-mediated killing, in order to correlate their sensitivities with LAK cell-tumor cell binding determined by flow cytometry, and also with expression of molecules putatively involved in both the adhesion and recognition process. Two cell adhesion molecules in the immunoglobulin supergene family lymphocyte function-associated antigen (LFA-3) and intercellular adhesion molecule (ICAM-1) expression by tumor cells were examined in detail with respect to the degree of LAK cell-tumor cell conjugation and cytotoxicity. LAK sensitivity of the tumor cell lines was not clearly related to the degree of binding and correlated most strongly with the level of LFA-3 expressed on these cell lines. Major histocompatability complex (MHC) Class I antigen (Ag) expression by tumors was also examined and correlated with an inhibitory effect on LAK cell-mediated killing. Interferon-gamma(IFN) treatment of two of these tumor lines decreased their sensitivity to LAK, and treated cells exhibited a higher level of MHC Class I Ag and ICAM-1 and an increased degree of conjugation with LAK cells. These findings demonstrate roles for LFA-3, ICAM-1, and MHC Class I expression in the LAK cell-tumor cell recognition and triggering of the lytic process.

Antigens, Surface

Gastroparesis in diabetics on chronic dialysis: clinical and laboratory associations and predictive features.

Clinical and laboratory features and risk factors for diabetic gastroparesis (DGP) were investigated in 226 diabetics on chronic dialysis; 106 subjects (43%) had DGP diagnosed by persistent vomiting improved with the use of prokinetic agents and 120 (control group) had no clinical DGP. Type 1 diabetics had DGP more frequently than type 2 diabetics (70 vs. 37%). The DGP group had longer duration of diabetes (21 +/- 8 vs. 13 +/- 6 years), higher frequency of diabetic orthostatic hypotension (95 vs. 33%), enteropathy (49 vs. 5%), blindness (52 vs. 23%), myocardial infarction (86 vs. 42%), extremity gangrene (54 vs. 27%) and cerebrovascular accidents (43 vs. 25%), lower serum albumin 32.3 +/- 3.9 vs. 35.4 +/- 3.8 g/l), urea (24.0 +/- 5.5 vs. 25.5 +/- 5.5 mmol/l) and creatinine (710 +/- 210 vs. 820 +/- 220 mumol/l), and higher serum TCO2 (20.9 +/- 3.1 vs. 19.8 +/- 2.7 mmol/l) than the control group (all differences significant at p +/- 0.004). Glycemic control was adequate in 24% of the DGP group subjects and 83% of the control subjects (p < 0.001). Annual hospitalization rate was 49 +/- 48 days/patient in the DGP group and 16 +/- 27 days/patient in the control group (p < 0.001). Median patient survival was 24 +/- 2 months in the DGP group and 61 +/- 9 months in the control group (p < 0.0001). Logistic regression identified long duration of diabetes and poor glycemic control as risk factors for DGP. In diabetics on dialysis, DGP is associated with high frequency of other diabetic complications, low serum albumin and creatinine, and high morbidity and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Is CT portography (CTAP) really useful in patients with liver tumors who undergo intraoperative ultrasonography (IOUS)?

The objectives were to compare the role of CT during arterial portography (CTAP) and intraoperative ultrasound (IOUS) in the management of patients with primary or metastatic liver tumors; to study the ability of CTAP to define resectability before laparotomy in these patients; and to study whether the omission of CTAP in the imaging algorithm resulted in a diminished resectability rate. Eighty-eight consecutive patients with primary or metastatic liver cancer who underwent CTAP and/or IOUS between January 1990 and December 1993 were reviewed. Thirty patients had both CTAP and IOUS and underwent 31 laparotomies (Group I). The sensitivity of these two tests to detect liver tumors was compared. Twenty-eight explorations were performed for hepatic metastases and three for hepatocellular carcinoma. Fifty-three patients, including those in group I, underwent CTAP before laparotomy and were studied to assess the sensitivity of CTAP in determining unresectability (Group II). Thirty-five patients (Group III) had IOUS only and were studied to determine whether the omission of CTAP decreased the resectability rate. In Group I, 52 hepatic lesions were found by a combination of imaging studies, operative exploration, and pathologic examination. The sensitivity of CT, CTAP, IOUS, and exploration were 67 per cent, 65 per cent, 100 per cent, and 75 per cent, respectively. IOUS was more sensitive than any other modality in detecting liver tumors (P < 0.001). It added new information in 7/31 cases (23%). The false positive rate of CTAP was 4/31 (13%). In one case (3%), a false positive result would have precluded a curative resection. CTAP changed management of 4/53 patients (7.5%) by showing unresectable disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

Preoperative chemoradiation for adenocarcinoma of the pancreas and duodenum.

PURPOSE: This study was designed to evaluate the effects of preoperative chemoradiation on resectability, response, local control, and survival in patients with local or local-regional involvement from carcinoma of the pancreas or cancer of the duodenum and to assess the associated toxicity of such treatment. METHODS AND MATERIALS: This prospective pilot study of preoperative chemoradiation was initiated in 1986 for patients with clinical evidence of adenocarcinoma of the pancreas or duodenum without evidence of distant metastases. Radiation was given at 1.8 Gy per day to a total dose of 50.4 Gy. Two cycles of chemotherapy were given concurrent with radiation. On days 2-5 and 29-32, 5-fluorouracil (1 gm/m2/24 h x 4 days) was given, while mitomycin-C (10 mg/m2) was given on day 2 only. Surgical resection was 4-6 weeks following completion of chemoradiation. Thirty-one patients (17 male and 14 female) were entered on the protocol with a median potential follow-up of 4.5 years (range 6 months to 7.5 years). The median age was 64 years (range 32-73 years). Twenty-seven patients had pancreatic cancer (25 head, two body), while four patients had carcinoma arising from the duodenum. Twenty-one patients were initially judged to be unresectable and ten potentially resectable prior to chemoradiation. RESULTS: Twenty-nine of 31 patients completed the entire course of radiation and both cycles of chemotherapy. Acute toxicity from chemoradiation consisted of nausea, vomiting, diarrhea, stomatitis, or hematologic suppression which was moderate to severe (Grade 3 or 4) in seven patients (23%). One patient died of sepsis following the first week of therapy. Seventeen patients (55%) underwent curative resection with subtotal or total pancreatectomy or Whipple resection (four duodenum, 13 pancreas) and two (2/17) had pathologic nodal involvement, while (0/17) none had involved margins. A complete pathologic response was seen in all four (4/4) patients with duodenal cancer and in none (0/13) with pancreatic cancer who underwent resection. The median postoperative hospitalization stay was 22 days (range 4-144 days). Of 17 patients who underwent curative resection, there were two postoperative mortalities (12%). Late complications have included abscess, one; and nonmalignant ascites, five. Ten of the 31 patients are alive. For patients with pancreatic cancer the median survival is 9 months, while survival at 1 year and 3 years are 36% and 19% overall and 60% and 43% at 1 and 3 years for those undergoing resection. Six of the 27 patients (22%) with pancreatic cancer are alive without recurrence. All four patients with duodenal cancer are alive without recurrence (12 months, 23 months, 35 months, 90 months). CONCLUSION: Preoperative chemoradiation for cancer of the pancreas and duodenal region was relatively well-tolerated and enhanced resectability and downstaging of nodal metastases were suggested. The 3-year survival, particularly in patients who underwent resection, was high. For these reasons the applicability of this treatment regimen for pancreatic cancer is presently being studied in a group-wide multi-institutional Phase II trial. Chemoradiation for duodenal cancer has produced a complete pathologic response in all patients and survival has been excellent, suggesting efficacy of this regimen for duodenal cancer.

Adenocarcinoma

Tc-99m sulfur colloid demonstration of diffuse pulmonary interstitial extramedullary hematopoiesis in a patient with myelofibrosis. A case report and review of the literature.

A 60-year-old man with a myeloproliferative syndrome and extramedullary hematopoiesis had progressive respiratory and cardiac insufficiency during the previous 18 months, with advancing interstitial pulmonary disease on chest x-ray. During analysis of his respiratory disease, results of a transbronchial biopsy showed interstitial involvement with increased numbers of megakaryocytes and other panhematopoietic staining elements. Results of a bone marrow scan demonstrated diffuse replacement of pulmonary interstitium with bone marrow, as a component of known ongoing extramedullary hematopoiesis.

Bone Marrow