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Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 613 records · Page 34Linked to original sources

Surgical management of pulmonary metastases.

Pulmonary metastases, especially solitary ones, have been managed surgically over the past 50 years. Resection is recommended for multiple metastases in patients who are capable of tolerating the required procedure, in which all pulmonary metastases can be resected as long as the primary site and extrapulmonary metastases are controlled or controllable, unless there is better treatment offering the same chance of cure for superior palliation. Complete resectability is the most important prognostic indicator, but several authors have found that for some tumors the number of pulmonary nodules, disease-free interval, and tumor doubling time are also important.

Adolescent↗

The effects of trypsin on ATP-sensitive potassium channel properties and sulfonylurea receptors in the CRI-G1 insulin-secreting cell line.

The effects of the proteolytic enzyme trypsin upon ATP-sensitive potassium (KATP) channel activity were examined in the CRI-G1 insulin-secreting cell line. Trypsin activated channels only when applied to the intracellular surface of the cell membrane. The activation could be prevented by the concomitant application of trypsin inhibitor or by heat inactivation of the enzyme. The trypsin-induced change in channel activity was accompanied by a reduction in the rate of channel rundown. However, trypsin did not affect the mean single channel conductance (55.2 pS), the ionic selectivity, or rectification of the KATP channel. Concentration response curves for various KATP channel inhibitors were constructed in the presence and absence of intracellular trypsin. The EC50 for tolbutamide was shifted from 30.0 +/- 4.5 microM, with 100 micrograms/ml heat-inactivated trypsin present to 9.7 +/- 1.0 mM with active trypsin in the intracellular solution. Treatment of the cells' external surface with 1 mg/ml trypsin did not alter the potency of tolbutamide. Intracellular trypsin also produced a significant fall in the potency of glibenclamide, meglitinide, and phentolamine but did not alter the effectiveness of thiopentone. Radioligand binding studies demonstrated a total loss of 3H-labeled glibenclamide binding when the intracellular surface of the cells was exposed to trypsin. In contrast, 3H-labeled glibenclamide binding was not affected when the enzyme was applied to the external surface. Trypsin treatment, therefore, alters a number of characteristics of KATP channel pharmacology, and we suggest that this is due to action at possibly more than one site but includes the functional cleavage of the sulfonylurea receptor from the KATP channel.

ATP-Binding Cassette Transporters↗

Head and neck cancer in blacks.

Our experience at University Hospitals of Cleveland (UHOC), Cuyahoga County, Ohio, led us to suspect an increased incidence of head and neck cancer in blacks. We reviewed our tumor registry records from 1975 to 1989 analyzing for age, sex, race, and head and neck site of disease. Head and neck cancers comprised 6.1% of all cancers at UHOC. This is in comparison with 3.7% of all cancers in Cuyahoga County and an estimated 5.5% nationally. This higher proportion of head and neck cancer was observed primarily in black men and women in whom these cancers made up 7.7% of all cancers compared with 5.7% in whites. Both black men and women had a higher percentage of these cancers out of all cancers for their respective sex and race than whites. For all head and neck cancer sites except the salivary glands, blacks were observed to be two to four times more likely than whites to be diagnosed before the age of 50 years (P < .01). These findings thus substantiated an increased incidence and earlier age of onset of head and neck cancers in blacks compared with whites.

Adult↗

All lactase preparations are not the same: results of a prospective, randomized, placebo-controlled trial.

OBJECTIVE: To compare the efficacy of three commercially available oral lactase preparations in adults with lactose intolerance. METHODS: Design--Prospective, randomized, placebo-controlled trial. Setting--Outpatient study in a General Clinical Research Center. Subjects--Ten lactose-intolerant healthy volunteers were challenged with ice cream containing 18 g of lactose. Lactase or placebo was given immediately prior to challenge. Measurements--Symptoms and breath hydrogen excretion were recorded for 3 h following lactose challenge. RESULTS: The three products differed in their abilities to influence symptoms and breath hydrogen excretion. Only Lactaid reduced the breath hydrogen excretion with lactose (mean peak, area under the curve and cumulative breath hydrogen excretion) (p < 0.05). Lactrase and Dairy Ease influenced symptoms: Lactrase reduced pain, bloating and total symptomatic scores (p < 0.05), whereas Dairy Ease only reduced pain (p < 0.05). Lactaid administration did not reduce symptoms. CONCLUSION: In lactose-intolerant subjects, the available lactase preparations differ in their ability to improve both breath hydrogen excretion and symptoms. Lactrase may be the product of choice for achieving symptomatic improvement.

Adult↗

Biokinetics of thallium-201 in normal subjects: comparison between adenosine, dipyridamole, dobutamine and exercise.

UNLABELLED: There are currently four common types of stress used with thallium-201 imaging in the diagnosis of coronary artery disease and risk assessment. The objective of this study was to examine the thallium biokinetics during exercise, adenosine, dipyridamole and dobutamine stress testing in 15 healthy volunteers. METHODS: Each subject underwent planar 201Tl imaging during maximal treadmill exercise testing, adenosine infusion (140 micrograms/kg/min for 6 min), dipyridamole infusion (142 micrograms/kg/min for 4 min) and dobutamine infusion (40 micrograms/kg/min). RESULTS: Absolute myocardial thallium activity was greater after pharmacologic testing than exercise, (p < 0.001 each). Thus, the activity was 505 counts/pixel with adenosine, 491 counts/pixel with dipyridamole, 517 counts/pixel with dobutamine and 409 counts/pixel with exercise. The myocardial thallium clearance was lower with pharmacologic testing than exercise; 9.7%/hr with adenosine, 9.9%/hr with dipyridamole, 11.3%/hr with dobutamine and 13%/hr with exercise (p < 0.01 each). The thallium uptake and clearance in the lung and liver were also greater with pharmacologic stress testing than exercise (p < 0.05). CONCLUSIONS: Thus, thallium biokinetics are different during pharmacologic stress testing with adenosine, dipyridamole and dobutamine than during exercise. Diagnostic criteria for quantitative analysis of myocardial perfusion imaging must therefore be specific for the type of stress used.

Adenosine↗

Chlorambucil induced apoptosis in chronic lymphocytic leukemia (CLL) and its relationship to clinical efficacy.

Chlorambucil induced apoptosis was measured in CLL cells treated with clinically achievable drug doses in vitro. While spontaneous apoptosis occurred in CLL cells incubated in vitro in the absence of drug, the level of apoptosis, as measured by the extent of DNA fragmentation, was greater in cells treated with chlorambucil. In addition, macrophages were shown to engulf drug treated CLL cells in vitro. To determine if chlorambucil can also induce apoptosis in vivo, CLL cells were isolated from patients before treatment and at intervals after clinical therapy with chlorambucil (0.9 mg/kg given over 3 days). Apoptosis was measured in these cells immediately after isolation and following incubation in vitro for 72 hr. No apoptotic changes were detected in cells immediately after isolation either before or after clinical treatment. In contrast, apoptosis was observed in cells that were incubated ex vivo for 72 hr, and the level of apoptosis was greater in cells that were isolated after chlorambucil treatment compared with cells obtained prior to therapy. The increased apoptosis observed in CLL cells ex vivo after therapy was related to the fall in the patient's lymphocyte count. In general, a large increase in apoptosis ex vivo after treatment was followed by a significant decrease in the patient's lymphocyte count. Thus, chlorambucil may produce its antitumor effect in CLL by inducing apoptosis-associated membrane changes that result in rapid clearance of the apoptotic cells by the immune system.

Apoptosis↗

Surface damage to cobalt-chrome femoral head prostheses.

Fifty-four cobalt-chrome alloy femoral heads were retrieved at revision surgery or at post-mortem; 23 came from uncemented, eight from hybrid and 23 from cemented hip arthroplasties. The uncemented and hybrid implants had porous coating, metal backing and modular femoral heads; with one exception none of the cemented implants had any of these. Twenty-five of the 31 heads from uncemented and hybrid arthroplasties, and 11 of the 23 heads from cemented arthroplasties showed surface damage involving more than 25% of the surface. Scanning electron microscopy revealed multidirectional fine scratches 1 micron to 10 microns in depth and width which appeared to have been made by fine, hard particles. There was a higher rate of such damage in the uncemented and hybrid arthroplasties than in the cemented implants, suggesting that the abrasive particles were mainly released from the metal, rather than from the cement or polyethylene components of the implants.

Adult↗

[Inhibitory effect of fentanyl citrate on endothelium-dependent relaxation in rat aorta].

We studied the effect of fentanyl on the endothelium-dependent vascular responses in isolated rat aortic strips. Fentanyl depressed the endothelium-dependent relaxation induced by acetylcholine but not that induced by the calcium ionophore, A23187. Endothelium-independent relaxation in response to sodium nitroprusside (SNP), a soluble guanylate cyclase activator, was not depressed by fentanyl. On the other hand, fentanyl depressed the increase in cyclic GMP level stimulated by acetylcholine but not that stimulated by A23187 or SNP. Furthermore, fentanyl depressed the vasocontraction by acetylcholine but not that by histamine or KCl in isolated pig coronary artery strips without endothelium, suggesting that fentanyl can inhibit endothelium-independent contraction via muscarinic receptor on smooth muscle cells. These results suggest that fentanyl can inhibit endothelium-dependent vasorelaxation via endothelium-derived relaxing factor (EDRF) by acting on endothelial cells but not on smooth muscle cells. The inhibitory effect of fentanyl on the relaxation probably occurs at the level of muscarinic receptor on endothelial cells or at a site before biochemical pathways converting L-arginine to EDRF.

Acetylcholine↗

Mg2+ modulates the binding of [3H]glibenclamide to its receptor in rat cerebral cortical membranes.

Radioligand binding studies were performed to determine the effect of various cations on the characteristics of [3H]glibenclamide binding to its high-affinity receptor in rat cerebral cortex membranes. Mg2+ was shown specifically to reduce radioligand binding to membranes pretreated with 5 mM EDTA. CaCl2 enhanced [3H]glibenclamide binding whilst MnCl2, KCl and NaCl were without significant effect. 2 mM MgCl2 induced a statistically significant rightward shift in the dissociation constant for glibenclamide obtained from both saturation and competition studies. These results suggest that Mg2+ may participate in the regulation of the sulphonylurea receptor in the rat cerebral cortex.

Animals↗

Late outcome and quality of life following percutaneous transluminal coronary angioplasty in octogenarians.

Limited data are available concerning the long-term survival and quality of life of octogenarians treated with percutaneous transluminal coronary angioplasty (PTCA). We retrospectively compared the results of PTCA in 118 octogenarians to that of 500 younger subjects. Among the octogenarians, long term follow-up was obtained including survival, relief of angina, assessment of quality of life, and capacity for independent living. These results were compared between men and women. The clinical success rate was 93% for the octogenarians and 88% for the younger patients (p = NS). The lesion success rates were 89% and 88% for these groups, respectively. Results of multilesion PTCA and dilatation of coronary occlusions were similar in both age groups. Major complication rates were 5.9% for the elderly and 3.8% for the younger patients (p < .008). Hospital mortality was higher among the octogenarians (4.6% vs 0.2%, p < .05). Among long-term octogenarian survivors, > 90% indicated a high level of satisfaction with their quality of life and health status. If needed, 88% would undergo the procedure again. Independent living was possible for 66% of these patients and automobile driving for 55%. Octogenarian men and women had similar baseline clinical characteristics, procedural success, complications, relief of angina, and survival. Women indicated a slightly lower level of satisfaction and capacity for independent living. PTCA can achieve a success rate in octogenarians comparable to that of younger patients but with an increased risk of serious complications. Patient satisfaction remains high and a majority of octogenarians remain physically active and capable of independent living.

Activities of Daily Living↗

Dibutyryl cyclic adenosine monophosphate differentially regulates cell proliferation in low and high alkaline phosphatase SaOS-2 human osteosarcoma cells: evidence for mediation by the insulin-like growth factor-II system.

In the present study, we have sought to determine whether a given signal transduction pathway can have diverse effects on subpopulations of cells of a lineage depending upon the stage of differentiation. To test this hypothesis, we selected the cyclic adenosine monophosphate (cAMP) signal transduction pathway because of its recognized importance in mediating the actions of many hormones, e.g., parathyroid hormone which acts on the bone-forming cells, the osteoblasts. Subpopulations of human osteosarcoma SaOS-2 cells with low (LSaOS) and high (HSaOS) alkaline phosphatase (ALP) content were chosen as model systems for preosteoblasts (pre-OB) and osteoblasts (OB), respectively. Dibutyryl cyclic AMP (DBcAMP) treatment of serum free cultures produced a differential effect on the proliferation of LSaOS cells (40 +/- 5% of control at 1 mM DBcAMP, P < 0.001) compared with HSaOS cells (no statistically significant effect). The finding supports the hypothesis. Next, we sought evidence for mediation, at least in part, by the insulin-like growth factor (IGF)-II regulatory system. We report that the basal expression of IGF-II, IGF binding protein (IGFBP)-3, and IGFBP-4 was higher in LSaOS cells than in HSaOS cells with the opposite true for type I IGF receptor. DBcAMP treatment of LSaOS cells decreased IGF-II and IGFBP-3 but increased IGFBP-4 and type I IGF receptor; no effect was observed for the type II IGF receptors. DBcAMP treatment of HSaOS cells had no detectable effect on IGF-II; IGFBP-3, or type I and type II IGF receptor expression; only IGFBP-4 expression increased with DBcAMP. These observations suggest that the differential regulation of cell proliferation by the cAMP signal transduction pathway may be mediated, at least in part, by the IGF-II regulatory system.

Alkaline Phosphatase↗

Utility of the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser for extensive pulmonary metastasectomy.

The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has been reported to have advantages in pulmonary resections including superior control of bleeding and air leak with relative sparing of pulmonary parenchyma. Extensive metastasectomies were performed in two patients with bilateral metastases who might have been excluded from surgery with other techniques. The patients were discharged within 8 days after uneventful postoperative courses. While this modality shows promise in permitting extensive metastasectomy, only long-term follow-up will demonstrate the ability to provide results comparable to those achieved with previous techniques.

Adult↗