Tonsil cryptolysis usingCO2 Swiftlase

Treatment for inflammation of the tonsils has taken a variety of therapeutic forms over the years, ranging from the application of iodine and massage in the preantibiotic era to the tonsillectomy, which prevails today. The architecture of the cryptic tonsil, its clinical implications, and the rationale for a conservative, yet effective treatment modality focusing on the tonsillar crypts are addressed in this article. Also described are the procedures and results of a retrospective clinical study in which conventional tonsillectomy was compared with CO₂ SwiftLase cryptolysis. Although our observations are not based on a prospective, controlled study, the information disseminated here may be useful to otolaryngologists who routinely perform tonsillectomy in their practice, using conventional surgical dissection methods or the CO₂ laser. According to our experience with a population of 120 patients, cryptolysis offers some clear advantages, particularly when performed with the SwiftLase apparatus. The procedure can be performed safely in an ambulatory surgery or office setting under local anesthesia. The cooperative patient avoids the cost and risks of general anesthesia. Limited tissue destruction significantly reduces operative and postoperative complications, discomfort, and recovery time. To conclude, CO₂ SwiftLase cryptolysis is a safe and cost-effective method of treating tonsil pathology without unnecessary sacrifice of the organ, and undue risks and expenses to the patient.^11,12     

Defective potassium currents in ataxia telangiectasia fibroblasts

Similarities exist between the progressive cerebellar ataxia in ataxia telangiectasia (AT) patients and a number of neurodegenerative diseases in both mouse and man involving specific mutations in ion channels and/or ion channel activity. These relationships led us to investigate the possibility of defective ion channel activity in AT cells. We examined changes in the membrane potential of AT fibroblasts in response to extracellular cation addition and found that the ability of AT fibroblasts to depolarize in response to increasing concentrations of extracellular K⁺ is significantly reduced when compared with control fibroblasts. Electrophysiological measurements performed with a number of AT cell lines, as well as two matched sets of primary AT fibroblast cultures, reveal that outward rectifier K⁺ currents are largely absent in AT fibroblasts in comparison with control cells. These K⁺ current defects can be corrected in AT fibroblasts transfected with the full-length ATM cDNA. These data implicate, for the first time, a role for ATM in the regulation of K⁺ channel activity and membrane potential.     

The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species

Ataxia-telangiectasia (A-T) is an autosomal recessive disorderinvolving cerebellar degeneration, immunodeficiency, radiationsensitivity, and cancer predisposition. A-T heterozygotes aremoderately cancer prone. The A-T gene, designated ATM, was recentlyidentified in our laboratory by positional cloning, and a partialcDNA clone was found to encode a polypeptide with a PI-3 kinasedomain. We report here the molecular cloning of a cDNA contigspanning the complete open reading frame of the ATM gene. Thepredicted protein of 3056 amino acids shows significant sequencesimilarities to several large proteins in yeast, Drosophilaand mammals, all of which share the PI-3 kinase domain. Manyof these proteins are involved in the detection of DNA damageand the control of cell cycle progression. Mutations in theirgenes confer a variety of phenotypes with features similar tothose observed in human A-T cells. The complete sequence ofthe ATM gene product provides useful clues to the function ofthis protein, and furthers understanding of the pleiotropicnature of the A-T mutations.     

Neurological Manifestations of COVID-19 Feature T Cell Exhaustion and Dedifferentiated Monocytes in Cerebrospinal Fluid

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The response of ataxia-telangiectasia homozygous and heterozygous skin fibroblasts to neocarzinostatin

Skin fibroblast strains from patients with ataxia-telangiectasia(A-T) were recently reported to be hypersensitive to the antitumorantibiotic neocarzinostatin (NCS). In this study, the distinctintermediate degree of NCS sensitivity previously shown withtwo strains of A-T heterozygous fibroblasts was extended andconfirmed in an additional eight strains. A sensitivity baselinefor A-T heterozygous cells has thus been established and mayserve for the laboratory diagnosis of A-T heterozygotes, a cancer-pronepopulation. The response of A-T homozygous and heterozygouscells to NCS was further characterized by two molecular parameters,DNA repair synthesis and inhibition of DNA replication. Thepattern of dose response with regard to DNA repair synthesis,as assayed by the benzoylated naphthoylated DEAE cellulose chromatographymethod, was similar in normal, A-T homozygous and A-T heterozygouscells, although certain variability between strains was observedwith regard to the amount of repair incorporation. This findingcorrelates with a similar observation made with the same cellstrains following -irradiation. Inhibition of DNA synthesisfollowing NCS treatment was reduced in A-T homozygous cells,as compared to normal cells, but the "Inhibition resistant"component of DNA synthesis typically observed following treatmentwith low doses of X-rays or bleomycin was not observed withNCS. A-T heterozygous cells showed somewhat less inhibitionof DNA synthesis than normal cells following NCS treatment,although this difference was small and was not significant enoughto serve as an additional laboratory diagnostic aid. It is concludedthat the reduced inhibition of DNA synthesis, rather than reducedextent of DNA repair synthesis, correlates with the cellularhypersensitivity of A-T homozygous cells. This hypersensitivityseems to be observed primarily, if not exclusively, with DNAbreaking agents.     

Additive value of low-dose dobutamine to technetium-99m sestamibi-gated single-photon emission computed tomography for prediction of wall motion improvement in patients undergoing coronary artery bypass graft

BACKGROUND: The two most useful methods for myocardial viability assessment are perfusion imaging and dobutamine echocardiography. HYPOTHESIS: The present study investigated the additive value of a new method, dobutamine technetium 99m (99mTc)-sestamibi-gated single-photon emission computed tomography (SPECT), which combines these two modalities, to the prediction of wall motion improvement after revascularization. METHODS: Fifty-five consecutive patients with ischemic cardiomyopathy, who were referred for viability evaluation, underwent resting and dobutamine (dose, 5-10 microkg/kg/min) gated SPECT with 99mTc-sestamibi. Of these patients, 36 underwent coronary artery bypass graft (CABG) within 1 month of the study and 32 had repeat resting gated SPECT within 1 year. Global and regional wall motion, wall thickness, and perfusion were simultaneously analyzed at rest and after dobutamine using the 20-segment model; the sestamibi uptake and wall motion response to dobutamine of each segment were rated quantitatively. Based on these findings, the segments were categorized as normal, viable, or nonviable. The predictive values for wall motion improvement were assessed by perfusion, using cutoffs of 50 and 60% of sestamibi uptake, and thereafter by the addition of dobutamine response in the segments that were rated nonviable. RESULTS: Of the 1,080 myocardial segments studied, 906 (84%) had abnormal wall motion and were analyzed for viability. Concordance between perfusion and wall motion response to dobutamine was 60% with the 50% cutoff of sestamibi uptake, and increased to 65% with the 60% sestamibi cutoff (p < 0.04). The respective predictive values of wall motion improvement using the 50 and 60% cutoff points were as follows: sensitivity 93 and 70%, respectively, (p < 0.01); specificity 59 and 86% (p < 0.001), respectively; accuracy 77% for both. The addition of the wall motion response to dobutamine to the assessment of the nonviable segments by perfusion (60% cutoff) increased the sensitivity from 70 to 85% (p = 0.001) and the negative predictive value from 70 to 81% (p = 0.009); the positive predictive value remained high (86 vs. 82%). No additive value of wall motion response to dobutamine was demonstrated for nonviable segments by perfusion with a 50% cutoff. CONCLUSION: Dobutamine sestamibi-gated SPECT is a feasible method for the analysis of myocardial perfusion, function, and contractile reserve of individual myocardial segments in patients with ischemic cardiomyopathy. Viability assessment based on a threshold of 60% uptake of sestamibi, with the addition of the wall motion response to dobutamine in the nonviable segments, seems to yield better predictive values for wall motion improvement after CABG.