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Biomedical subjects

Daniel Choi

Publications and source records attributed to Daniel Choi.

5 recordsLinked to original sources

Type 1 interferon perturbates clonal competition by reshaping human blood development.

Inflammation accelerates evolutionary dynamics of hematopoietic stem cells (HSCs) in clonal hematopoiesis and myeloid neoplasms. We studied HSCs, progenitors and immune cells from patients with myeloproliferative neoplasms at baseline and following interferon-α (IFNα) treatment, the only therapy to deplete mutated stem cells. We deployed single-cell multiomics methods that distinguish the IFNα effects on mutated stem cells from the admixed wild-type HSCs, with respect to their differentiation, transcriptomes, immunophenotypes and chromatin accessibility. IFNα simultaneously activated HSCs into two polarized states: a lymphoid progenitor expansion associated with an anti-inflammatory state and an inflammatory myeloid progenitor state derived from HSCs. The augmented lymphoid differentiation balanced the typical myeloproliferative-neoplasm-induced myeloid bias, associated with normalized blood counts. Somatic mutations modified the effects of IFNα on HSC differentiation and cell cycle entry rates. Clonal fitness upon IFNα exposure was due to resistance of CALR- or JAK2-mutated stem cells to differentiate into inflammatory myeloid progenitors.

Journal Article↗

Early carotid endarterectomy after acute stroke.

PURPOSE: Carotid endarterectomy (CEA) after acute stroke is generally delayed 6 to 8 weeks because of fear of stroke progression. This delay can result in an interval stroke rate of 9% to 15%. We analyzed our results with CEA performed within 1 to 4 weeks of stroke. METHODS: Records for all patients undergoing CEA after stroke between 1980 and 2001 were analyzed. Perioperative evaluation included carotid duplex scanning or angiography, and head computed tomography or magnetic resonance imaging. All patients with nonworsening neurologic status, additional brain territory at risk for recurrent stroke, and severe ipsilateral carotid stenosis underwent CEA. Patients were grouped according to time of CEA after stroke: group 1, first week; group 2, second week; group 3, third week; group 4, fourth week. Statistical analysis was performed with the chi(2) test, logistic regression, and analysis of variance. RESULTS: Two hundred twenty-eight patients underwent CEA within 1 to 4 weeks of stroke. Perioperative permanent neurologic deficits occurred in 2.8% of patients in group 1 (72 procedures), 3.4% of patients in group 2 (59 procedures), 3.4% of patients in group 3 (29 procedures), and 2.6% of patients in group 4 (78 procedures). There was no relationship between location or size of preoperative infarct and time of surgery. Only preoperative infarct size correlated with probability of neurologic deficit after CEA (P <.05). CONCLUSION: Incidence of postoperative stroke exacerbation is similar at all intervals. The results are within acceptable limits for treatment of symptomatic carotid stenosis. CEA may be performed within 1 month of stroke with similar results at all intervals during this period.

Acute Disease↗

Should ruptured abdominal aortic aneurysms be repaired in the octogenarian?

PURPOSE: Several investigators have suggested a dismal prognosis of ruptured abdominal aortic aneurysm (rAAA) repair in the elderly. The purpose of this study is to evaluate the morbidity and mortality of rAAA repair in octogenarians and compare it to that of a younger population. METHODS: From 1980 to 2000, all patients undergoing emergent rAAA repair were divided into two groups based on their age; Group I: age <80, Group II: > or =80 years. Outcomes were evaluated based on a Chi-square test and a P-value <0.05 indicated statistical significance. RESULTS: Over a 20-year period, 323 patients underwent rAAA repair through a left retroperitoneal (74%) or standard transperitoneal (26%) approach. In Group I (age <80 years) and II (> or =80 years), the overall 30-day mortality was 25 and 41% (P<0.05), respectively. Furthermore, the elderly population had a higher incidence of death due to myocardial infarction (15 vs. 7%), as well as non-fatal cardiac and cerebrovascular events (17 vs. 4%) when compared to the younger patients. CONCLUSION: Although the elderly patients have an increased risk of having cardiac and cerebrovascular events in the postoperative period, the treatment of rAAAs in these patients should not be any different than that of a younger population. The left retroperitoneal approach is feasible and beneficial for rAAA repair and is associated with a limited morbidity and mortality.

Age Factors↗

Carotid-carotid crossover bypass: is it a durable procedure?

PURPOSE: Reconstruction of a diseased common carotid artery may necessitate direct repair via aortic artery-based revascularization. However, carotid-carotid artery crossover grafting is an alternative extra-anatomic option that obviates the need for median sternotomy. We analyzed our results with carotid-carotid artery crossover bypass surgery. METHODS: Data were analyzed for all patients undergoing carotid-carotid crossover bypass surgery from 1995 to 2000. Data on patient demographics, indications for surgery, perioperative morbidity and mortality, and graft patency were retrieved from a vascular surgery data base and hospital records. Stroke-free survival and graft patency were determined with life table methods. RESULTS: Over 5 years, 24 carotid-carotid artery crossover bypass procedures were performed to treat both symptomatic (n = 19, 79%) and asymptomatic (n = 5, 17%) disease. Nine procedures (38%) were performed in men, 3 (13%) in patients with diabetes, 12 (50%) in active smokers, and 2 in patients with a history of Takayasu arteritis. Patient mean age was 63 years (range, 38-79 years). Twenty-three patients (96%) received polytetrafluoroethylene conduit grafts, and the remaining patients received vein grafts. Ten (42%) patients underwent concomitant endarterectomy. There were no perioperative deaths. One patient (4%) had asymptomatic early occlusion, one had transient neurologic deficit (4%), one (4%) required additional surgery because of bleeding, and one (4%) had a perioperative cerebrovascular accident (stroke). Three (17%) asymptomatic late occlusions were identified at 11, 57, and 64 months, respectively. Mean follow-up was 30 months (range, 1-70 months). Primary patency was 88%, and secondary patency was 92% at 3 years. Stroke-free survival was 94% at 4 years. CONCLUSION: Carotid-carotid artery crossover bypass surgery is a safe and durable procedure. Its use precludes the need for median sternotomy and provides acceptable stroke-free survival.

Adult↗

Dynamic changes in acetylcholine output in the medial striatum during place reversal learning.

The present studies explored the role of the medial striatum in learning when task contingencies change. Experiment 1 examined whether the medial striatum is involved in place reversal learning. Testing occurred in a modified cross-maze across two consecutive sessions. Injections of the local anesthetic, bupivacaine, into the medial striatum, did not impair place acquisition, but impaired place reversal learning. The reversal-learning deficit was due to an inability to maintain the new choice pattern following the initial shift. Experiment 2 determined whether changes in acetylcholine (ACh) output occur during the acquisition or reversal learning of a place discrimination. Extracellular ACh output from the medial striatum was assessed in samples collected at 6-min intervals using in vivo microdialysis during behavioral testing. ACh output did not change from basal levels during place acquisition. During reversal learning, ACh output significantly increased as rats began to learn the new choice pattern, and returned to near basal levels as a rat reliably executed the new place strategy. The present results suggest that the medial striatum may be critical for flexible adaptations involving spatial information, and that ACh actions in this area enable the shifting of choice patterns when environmental conditions change.

Acetylcholine↗