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Biomedical subjects

Michael Kim

Publications and source records attributed to Michael Kim.

15 recordsLinked to original sources

Claudication secondary to Perclose use after percutaneous procedures.

The use of suture-mediated arterial closure devices has dramatically increased with the increased number of percutaneous procedures being performed. Complications from suture-mediated closure devices have been underreported. Specifically, arterial stenosis resulting in claudication has not been previously described in detail. We present nine patients who presented with various leg symptoms after Perclose was used to achieve arterial hemostasis following percutaneous procedures. All cases were found to have significant arterial stenoses from the Perclose sutures. Once diagnosis was correctly made, the patients either underwent surgical repair or percutaneous balloon angioplasty and in all cases the symptoms abated.

Adult↗

Platelet Toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo.

Toll-like receptors (TLRs) play a critical role in stimulating innate immunity by recognizing pathogen-associated molecular patterns (PAMPs) on invading microorganisms. Platelets also play a role in innate immunity, and we studied whether they express TLR. Results show that human and murine platelets variably expressed TLR2, TLR4, and TLR9 by flow cytometry and Western blotting. TLR4 expression was confirmed by demonstrating murine platelet binding to lipopolysaccharide (LPS). Thrombin activation of the platelets significantly enhanced the expression of TLR9, suggesting that at least some TLRs may derive from intracellular compartments. When LPS was administered to LPS-sensitive C3H/HeN and LPS-resistant C3H/HeJ mice, functional TLR4 expression in vivo was shown to be responsible for LPS-induced thrombocytopenia. However, when the C3H/HeN mice were first rendered thrombocytopenic by an antiplatelet antibody and then administered LPS, a significant reduction occurred in their ability to produce TNF-alpha. The decreased cytokine production in the thrombocytopenic mice was restored with platelet transfusion. These results suggest that platelets express various TLRs and that the functional significance of one of these, TLR4, appears to be a role in the modulation of LPS-induced thrombocytopenia and TNF-alpha production. This work implicates platelets as important mediators of innate immune responses against invading microorganisms.

Animals↗

Fibrosis progression in chronic hepatitis C patients with occult hepatitis B co-infection.

Occult hepatitis B virus (HBV) infection in individuals without hepatitis B surface antigen (HBsAg) can be identified in hepatitis C virus (HCV) infected patients. However, its role in fibrosis progression remains uncertain. This retrospective study compared the fibrosis progression (defined as fibrosis progression by at least one stage) and progression to severe fibrosis (fibrosis stage 3 or 4) in HCV patients with occult HBV infection. Occult HBV infection was diagnosed by the detection of HBV DNA in the serum of 74 consecutive anti-HCV positive patients by PCR. Thirty-one patients (41.9%) had occult HBV infection. All 74 patients had a median of 2 (range 2-3) liver biopsies. The median time between the first and last liver biopsy was 57.7 (range 15.0-132.8) months. Eleven of the 31 patients with occult HBV infection compared with 12 of the 43 patients without occult HBV infection had fibrosis progression (35.5% versus 27.9%, respectively, p=0.608). Six of the 31 patients with occult HBV infection compared with 8 of the 43 patients without occult HBV infection developed severe fibrosis (19.4% versus 18.6%, respectively, p=0.946). In conclusion, chronic HCV patients with occult HBV co-infection does not seem to progress more than patients without occult HBV infection. However, more large-scale studies are needed before a definite conclusion can be obtained.

DNA, Viral↗

Effect of short pulse width programming in AutoCapture devices.

Pacing chronaxie can increase over time. The impact of a short pulse duration on threshold (THR) variations, frequency of noncapture episodes, and overall patient safety has not been fully studied. AutoCapture (AC) pacemakers are capable of memorizing THR trends and loss of capture (LOC) episodes. The study included 20 recipients of AC pacemakers (mean age = 76 +/- 9 years, 15 men) followed for 6 months. They were randomly assigned to pulse durations of 0.2 versus 1.0 ms at 1 month, and crossed over to the alternate programming at 3 months. Evoked response (ER) and AC tests were performed at follow-up. At 0.2 ms and 1.0 ms, the mean number of LOC/day was 2.37 +/- 5.81 and 0.91 +/- 0.49, respectively (ns). LOC trends between follow-up were significantly different with 0.2 versus 1.0 ms pulse duration (P < 0.01). AC THR at 1.0 ms was significantly lower (0.44 +/- 0.77) than at 2.0 ms (0.97 +/- 0.26, P < 0.05). No patient reported symptoms related to LOC during the study. Pulse duration programmed near the strength-duration curve is associated with greater variations in THR and LOC. AC responds to these changes by delivering 4.5 V pulses and keeping the capture THR at low, though safe values.

Aged↗

Intracoronary brachytherapy for in-stent restenosis using long sources reduces restenosis.

Edge restenosis (candy wrapper effect) and late thrombosis remain a problem in various randomized intracoronary brachytherapy (ICBT) trials for the treatment of in-stent restenosis (ISR). Target vessel revascularization (TVR) due to target lesion revascularization (TLR) and edge restenosis can be decreased with the use of longer ICBT sources and debulking devices and has not been systematically studied. We analyzed 226 patients with ISR (240 vessels of 264 lesions; average lesion length 17.5+/-8.9 mm) who had lesion debulking followed by 90 Strontium (Sr) beta-irradiation using the Novoste Betacath system (30 mm source in 144 vessels and 40 mm source in 96 vessels). Dual antiplatelet therapy was recommended for one year. At follow-up of 12+/-2 months, clinical TVR occurred in 9.7%, with TLR in 7.1% and non-TLR in 2.6% of cases. There was no delayed or late subacute thrombosis. Beta-irradiation using a longer 90Sr source after lesion modification with cutting balloon (CB) and or rotational atherectomy (RA), along with the use of long-term dual antiplatelet therapy is safe and associated with single-digit clinical restenosis.

Angioplasty, Balloon, Coronary↗

Elevated homocysteine levels in patients with end-stage renal disease.

PURPOSE: To examine the effect of hemodialysis on plasma homocysteine levels, and the relationship of these values to clinical cardiovascular events in patients with end-stage renal disease (ESRD). METHODS: Adults undergoing chronic hemodialysis were studied at baseline and at six months. Their clinical histories were obtained at the baseline visit, and measurements of plasma homocysteine concentration were made immediately prior to and following routine dialysis. The occurrence of clinical cardiovascular events was assessed over six months. RESULTS: We enrolled 147 patients (85 men and 62 women, age 58 +/- 15 years) who required hemodialysis for 3.4 +/- 3.4 years (mean +/- SD). The median homocysteine level for this population (including both pre- and post-dialysis values) was 17.3 micromoles/L. Mean pre-dialysis plasma homocysteine levels of patients with clinical cardiovascular disease did not differ significantly from those without the disease (22.5 +/- 9.9 vs. 25.4 +/- 24.5 micromoles/L, respectively), nor did post-dialysis levels differ between these populations. During six months follow-up, rates of ischemic events were not related to hyperhomocysteinemia. The difference between mean pre- and post-dialysis homocysteine levels (26.3 +/- 19.7 and 15.6 +/- 11.4 micromoles/L, respectively) and the decline in homocysteine over the course of a single dialysis treatment session (10.3 +/- 10.2 micromoles/L) were highly significant (p<0.0005). CONCLUSIONS: Plasma homocysteine levels were elevated in 82% of 147 patients with ESRD and fell to the normal range in a majority of patients during a single dialysis treatment session. Mean pre-dialysis levels did not change significantly over six months, however, and plasma homocysteine levels did not predict cardiovascular events in this population. There was also a trend towards worse outcomes in patients with lower homocysteine levels, which correlates to findings from recent studies. Further studies are needed to clarify the association between hyperhomocysteinemia and coronary risk in patients with ESRD.

Adult↗

Idiopathic sclerochoroidal calcification.

BACKGROUND: Idiopathic sclerochoroidal calcification (ISC) is an uncommon condition of calcium deposition at the level of the sclera and choroid of the posterior pole. With normal acuity and visual field, it typically manifests in asymptomatic older males. It can be diagnosed on clinical grounds, appearing as multiple geographic, yellowish, placoid-like lesions in the sclera and choroid, commonly found in the superotemporal arcade of the midperipheral fundus in both eyes. Ocular ultrasound and fluorescein angiography have classic results. CASE REPORT: An 85-year-old white man came to us for routine examination. Best-corrected visual acuity was 20/40 O.D. and O.S. Dilated fundus examination revealed several midperipheral yellowish-white deposits with retinal pigment epithelium hyperpigmentation temporally in each eye. Ocular ultrasound revealed high reflectivity consistent with calcium. The lesions demonstrated mild hyperfluorescence in the late phase of fluorescein angiography. Laboratory testing was void of abnormal calcium or phosphorous metabolism, and a diagnosis of ISC was made. CONCLUSION: Idiopathic sclerochoroidal calcification is a benign lesion of calcium deposition in the posterior pole, often discovered on routine examination. Although it is idiopathic, systemic evaluation is warranted to rule out dystrophic or metastatic calcification by various pathological conditions associated with abnormal calcium-phosphorus metabolism--most notably, hyperparathyroidism. Differential diagnoses include choroidal osteoma, melanoma, and metastatic carcinoma.

Aged↗

Inhibition of xenogeneic GVHD by PEN110 treatment of donor human PBMNCs.

BACKGROUND: Development and characterization of methods for preventing transfusion-associated GVHD have utilized in vitro studies with human WBCs and in vivo studies in animal models. The limitation of these assays is that the in vivo GVHD response of treated human WBCs has not been tested directly. STUDY DESIGN AND METHODS: PBMNCs isolated from nonleukoreduced RBC units exposed to gamma irradiation, treated with PEN110 or PBS, were tested for their ability to induce xenogeneic GVHD when injected into severe combined immunodeficient (SCID) mice. RESULTS: These studies showed that the SCID mice injected with PBS-treated PBMNCs developed serum levels of human immunoglobulin that were followed by weight loss and display of ruffled fur characteristic of xenogeneic GVHD in these mice. In contrast, SCID mice injected with PEN110-treated or gamma-irradiated PBMNCs did not exhibit any of these responses. CONCLUSIONS: In these studies PEN110 treatment and gamma irradiation were equally effective at preventing in vivo GVHD responses when the treated cells were injected into SCID recipients. These results are consistent with previous results obtained when these two treatment methods were compared with in vitro studies with PBMNCs and in vivo studies in mouse models.

Animals↗

Death-associated protein kinase promoter hypermethylation in normal human lymphocytes.

A high frequency of death-associated protein kinase (DAPK) promoter hypermethylation has been noted in B-cell malignancies, head and neck cancers, and other solid tumors, and it has been used as a tumor marker in molecular detection strategies. Low levels of DAPK promoter hypermethylation, ranging from 0.003 to 1.181%, were detected in peripheral blood cells from 75 of 143 (52%) normal subjects by quantitative methylation-specific PCR (Q-MSP). In 10 of 10 selected patients, MSP amplification of a portion of the DAPK promoter followed by PCR product sequencing confirmed dense hypermethylation of the CpG island in their peripheral blood cells. Q-MSP analysis of fluorescence-activated cell-sorted peripheral blood cells from three of these patients demonstrated that a significantly greater proportion of B cells (1.074-6.026%) were DAPK hypermethylated than were T cells, monocytes, or neutrophils, which were <0.06% hypermethylated. Further analysis after sorting of one subject's B cells into IgM+, IgM-, IgG+, and IgG- subpopulations demonstrated that DAPK hypermethylation was predominantly present in the IgM- compared with IgM+ B cells (3.338% versus 0.436%). DAPK promoter hypermethylation was found in IgM- B cells in normal individuals. The same hypermethylation identified in B-cell malignancies may reflect a clonal outgrowth of B cells arising from this compartment and may indicate a susceptibility to neoplastic transformation in a subset of B cells. Normal circulating lymphocytes with DAPK promoter hypermethylation may act as confounding factors in tumor detection based on DAPK hypermethylation.

Apoptosis Regulatory Proteins↗

Effect of ethnicity and race on the use of pain medications in children with long bone fractures in the emergency department.

STUDY OBJECTIVES: We characterize the use of analgesics among children of different race and ethnicity who had isolated long bone fractures that were treated in emergency departments (EDs) across the United States. METHODS: According to ED survey data from the National Hospital Ambulatory Medical Care Survey for 1992 through 1998, patients younger than 19 years and visiting EDs with isolated long bone fractures were identified by International Classification of Diseases, Ninth Revision codes. Analgesic-prescribing rates were examined for children of different racial and ethnic groups. Multivariate logistic regression was used to determine the independent effect of race and ethnicity on analgesic use and on opioid use while other potential confounders were controlled. RESULTS: One thousand thirty records representing approximately 3.9 million children were identified. Seven hundred ninety-two records were of non-Hispanic white patients, 111 were of black patients, and 127 were of Hispanic white patients. No significant difference was noted among the different racial and ethnic groups for receipt of analgesic medications or of opioid analgesic medications. Children with long bone fractures who visited the ED in the South (adjusted odds ratio [OR] 1.91; 95% confidence interval [CI] 1.19 to 3.09) and the West (adjusted OR 1.78; 95% CI 1.07 to 2.96) received opioid analgesic medications more often than children in the Northeast. Children in the South also received any analgesics more often (adjusted OR 1.61; 95% CI 1.01 to 2.56). CONCLUSION: No difference in analgesic prescription or opioid analgesic prescription was found between black and Hispanic children compared with non-Hispanic white children with long bone fractures in EDs. There are, however, previously unreported regional differences in analgesic administration.

Adolescent↗

Gamma-globulins prepared from sera of multiparous women bind anti-HLA antibodies and inhibit an established in vivo human alloimmune response.

It has previously been shown that sera from multiparous women have increased levels of anti-idiotypic antibodies specific for anti-HLA molecules. gamma-Globulins prepared from these sera may be superior to commercial preparations of intravenous gamma-globulin (IVIg) for inhibiting HLA alloimmunization. To test this, F(ab')2 fragments prepared from either commercial IVIg or from the sera of men or multiparous women were coupled to CNBr-Sepharose and tested for their ability to bind F(ab')2 fragments derived from polyspecific anti-HLA sera. As determined by flow cytometry, compared with columns coated with F(ab')2 derived from commercial IVIg or sera from men, columns coated with F(ab')2 prepared from the sera of multiparous women bound significantly more anti-HLA. In addition, intact IgG molecules prepared from the sera of multiparous women significantly neutralized the reactivity of the anti-HLA F(ab')2 fragments. To determine whether the intact IgG molecules or their corresponding F(ab')2 fragments could affect in vivo alloimmunity, they were tested for their ability to inhibit an established IgG human alloimmune response in humanized severe combined immunodeficient (SCID) mice. Compared with commercial IVIg, when intact IgG or F(ab')2 fragments derived from multiparous women were administered to SCID mice making human anti-HLA antibodies, a significant reduction in anti-HLA reactivity was observed. The findings suggest that IgG molecules prepared from the sera of multiparous women have increased anti-idiotypic reactivity against anti-HLA antibodies, which can significantly inhibit an established human IgG alloimmune response in an Fc-independent manner.

Animals↗

Long-term effects of Le Fort I osteotomy for resection of juvenile nasopharyngeal angiofibroma on maxillary growth and dental sensation.

OBJECTIVE: To analyze the long-term effects of the Le Fort I osteotomy approach for the resection of juvenile nasopharyngeal angiofibroma (JNA) on maxillary growth and dental sensation. DESIGN: Prospective collection of structured data. SETTING: Tertiary care academic teaching hospital. PATIENTS: Between 1993 and 1998, 5 adolescents (aged 10-14 years) constituted the evaluable cohort among 14 patients who underwent Le Fort I osteotomy for JNA resection. Mean follow-up was 47.2 months. INTERVENTIONS: The Le Fort I osteotomy approach was used to resect JNA. Cephalometric x-ray films were taken at various postoperative intervals to assess maxillary growth. The results were matched against age-correlated predictions from Dentofacial Planner software. MAIN OUTCOME MEASURES: Horizontal and vertical maxillary growth were each measured anteriorly and posteriorly by comparing interval postoperative cephalometric x-ray films. Dental sensation was longitudinally evaluated by performing interval pulp testing postoperatively. RESULTS: (1) Average vertical growth of the maxilla achieved 30% of predicted growth anteriorly (P =.02). (2) Average horizontal growth matched predicted growth in all patients. (3) All patients demonstrated long-term maxillary dental denervation. CONCLUSIONS: Le Fort I osteotomy provides excellent surgical exposure for resection of JNA in the growing facial skeleton. Although it significantly affects vertical but not horizontal growth, its cosmetic effect is negligible. It also causes long-term dental denervation, which in most cases is undetected by patients.

Adolescent↗

A protocol for prevention of radiographic contrast nephropathy during percutaneous coronary intervention: effect of selective dopamine receptor agonist fenoldopam.

Radiographic contrast nephropathy (RCN), acute worsening of renal function due to contrast agents, can occur in 15%-40% of patients with baseline renal dysfunction undergoing percutaneous coronary intervention (PCI) and is associated with increased morbidity and in-hospital mortality. The purpose of this study was to evaluate whether the selective dopamine-1 (DA-1) receptor agonist fenoldopam would be beneficial in patients with chronic renal insufficiency (CRI) undergoing PCI and also to design a protocol for prevention of RCN. We analyzed 150 consecutive patients with CRI [baseline serum creatinine (BSCr) +/- 1.5% mg] who underwent PCI and received fenoldopam during and after the procedure, in addition to saline hydration. RCN, defined as > 25% increase of BSCr 48-72 hr after PCI, occurred in 4.7% (n = 7) of 150 PCI patients receiving fenoldopam and 3.5% in diabetics (n = 85) vs. 6.1% in nondiabetics (n = 65; P = NS). No patients required dialysis. The observed 4.7% incidence of RCN with fenoldopam was significantly lower than 18.8% incidence in the historical control group (P < 0.001). Our data suggest that fenoldopam is a useful adjunct in the prevention of RCN during PCI, especially in diabetics.

Aged↗

Emerging topics in the regulation of leukocyte transendothelial migration.

This year marks the 50th Anniversary of the founding of the Microcirculatory Society. Since the formation of this society this field has witnessed tremendous progress in understanding the process of leukocyte recruitment during inflammation, injury, and immune reactions. This topic has been an important focus of many of the members of the Microcirculatory Society as well as our colleagues worldwide. The goal of this brief review is to bring attention to a few emerging topics in inflammation research. Here the focus is on one particular model of how one leukocyte type (PMN) can regulate the recruitment of a second different leukocyte type (T cell) and provide an outline of other aspects that bear on spatial and temporal behavior of specific leukocyte and endothelial cell adhesion molecules during leukocyte transmigration under dynamic shear flow in vitro.

Animals↗