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Biomedical subjects

V A Kumar

Publications and source records attributed to V A Kumar.

14 recordsLinked to original sources

CT assessment of vocal cord medialization.

BACKGROUND AND PURPOSE: Unilateral vocal cord paralysis (UVCP) occurs after iatrogenic injury or disease process and is associated with dysphonia and aspiration. Various surgical options are available for treatment of UVCP, including vocal cord medialization thyroplasty and injection laryngoplasty. These augmentative procedures improve phonation and airway protection. Our purpose was to demonstrate the CT appearance of implants used for the treatment of UVCP. METHODS: Twelve patients treated surgically for UVCP were studied with helical CT. The vocal cords were augmented by using Silastic implants (n = 7), polytetrafluoroethylene (Gore-Tex) implants (n = 2), Teflon injections (n = 2), or fat injection (n = 1). Augmented vocal cords were characterized by size, shape, and Hounsfield units (HU). Two other patients with failed medialization thyroplasty were evaluated for the position of the extruded implant relative to the paralyzed vocal cord. RESULTS: The 7 Silastic implants were triangular and hyperattenuated (293.4 +/- 90.4 HU). The 2 Gore-Tex implants were heterogeneous with lobulated medial margins and were hyperattenuating (320 and 414 HU). The injected materials demonstrated ovoid/masslike configurations: the 2 Teflon injections were hyperattenuated (107 and 429 HU), and the fat injection was hypoattenuated (-102 HU). Inferior displacement of the implant was demonstrated relative to the true vocal cord in 2 patients with failed Silastic thyroplasties. CONCLUSION: CT can distinguish various types of vocal cord augmentation. Silastic implants are recognized by their characteristic triangular configuration. The Gore-Tex implants had unique heterogeneous attenuation with lobulated medial margins. Fat and Teflon injections both appear ovoid/masslike. Teflon injection should not be mistaken for tumor.

Adipose Tissue↗

Extended daily dialysis vs. continuous hemodialysis for ICU patients with acute renal failure: a two-year single center report.

Extended daily dialysis (EDD) is an easily implemented alternative to continuous renal replacement therapy (CRRT) in the intensive care unit (ICU). Since EDD offers most of the advantages of CRRT, we sought to compare the effectiveness of these two modalities. In this 2-year study, 54 ICU patients with ARF were treated with either continuous hemodialysis (CHD) or EDD. Oliguria was present in 64% of patients who received CHD vs. 73% of EDD patients (p=NS) while 93% of CHD and 81% of EDD patients required mechanical ventilation (p=NS). Patients treated with EDD were younger than those who received CHD (47.0 +/- 12.6 vs. 56.7 +/- 13.7, p=0.009), but there were no significant differences in gender or mean APACHE II scores at the time of randomization. Mean arterial blood pressures measured during treatment were maintained between 70 and 80 mmHg for both EDD and CHD and average daily serum electrolyte levels fell within normal ranges for EDD and CHD. Average daily fluid input and output were 5.8 +/- 3.3 L and 6.0 +/- 3.2 L for CHD vs. 3.3 +/- 2.6 and 3.0 +/- 1.7 L for EDD after exclusion of data from 2 burn patients. Hourly heparin anticoagulation rates were 1080 U/hour for CHD and 643 U/hour for EDD, p=0.02. Anticoagulation-free treatments were performed during 43% of all EDD treatments vs. 21% of all CHD treatments, p<0.001. Clotting of the dialyzer or circuit occurred at least once during 51% of all CHD treatment days vs. 22% of EDD treatments (p<0.001). We conclude that EDD is a safe, effective alternative to CRRT that offers comparable hemodynamic stability and excellent small solute control.

Acute Kidney Injury↗

Extended daily dialysis: A new approach to renal replacement for acute renal failure in the intensive care unit.

Continuous venovenous hemofiltration (CVVH) is an effective form of renal replacement therapy for acute renal failure (ARF) that offers greater hemodynamic stability and better volume control than conventional hemodialysis in the critically ill, hypotensive patient. However, the application of CVVH in the intensive care unit (ICU) has several disadvantages, including intensive nursing requirements, continuous anticoagulation, patient immobility, and expense. We describe a new approach to the treatment of ARF in the ICU, which we have termed extended daily dialysis (EDD). In this study, EDD was compared with CVVH in 42 patients: 25 patients were treated with EDD for a total of 367 treatment days, and 17 patients were treated with CVVH for a total of 113 days. Median treatment time per day was 7.5 hours for EDD (range, 6 to 8 hours, 25th to 75th percentile) versus 19.5 hours for CVVH (range, 13.4 to 24 hours; P < 0.001). Mean arterial blood pressures (MAPs) did not differ significantly for patients treated with EDD when measured predialysis (median MAP, 70 versus 67 mm Hg for CVVH; P = 0.078), midway through daily treatment (70 versus 68 mm Hg for CVVH; P = 0.083), or at the end of treatment (71 versus 69 mm Hg for CVVH; P = 0.07). Net daily ultrafiltration was similar for the two treatment modalities (EDD, median, 3,000 mL/d; range, 1,763 to 4,445 mL/d; CVVH, 3,028 mL/d; range, 1,785 to 4,707 mL/d; P = 0.514). Anticoagulation requirements were significantly less for patients treated with EDD (median dose of heparin, 4,000 U/d; range, 0 to 5,800 U/d versus 21,100 U/d; range, 8,825 to 31,275 U/d for patients treated with CVVH; P < 0.001). We found that EDD eliminated the need for constant supervision of the dialysis machine by a subspecialty dialysis nurse, allowing one nurse to manage more than one treatment. Overall, EDD was well tolerated by the majority of patients, offered many of the same benefits provided by CVVH, and was technically easier to perform.

Acute Kidney Injury↗

Spermine conjugated peptide nucleic acids (spPNA): UV and fluorescence studies of PNA-DNA hybrids with improved stability.

Peptide Nucleic Acids (PNAs), the achiral DNA mimics with amide backbone, are emerging as attractive leads for drug development by antisense approach. Two major limitations of PNAs from an application perspective are their limited solubility in aqueous systems and pronounced self-organization. In this paper, it is shown that covalent conjugation of spermine at C-terminus of PNA (spPNA) improves its solubility and binds to complementary DNA 20 times stronger than the corresponding binding of PNA. Fluorescence kinetics shows a 2 fold acceleration of the bimolecular association process in spPNA:DNA hybrids, due to electrostatic interaction cationic spermine tagged to PNA with anionic DNA. This modification is easy to incorporate into PNA synthetic protocols to make them more effective in biological applications and may improve the poor cell uptake of PNA.

DNA↗

Triplex formation at physiological pH by 5-Me-dC-N4-(spermine) [X] oligodeoxynucleotides: non protonation of N3 in X of X*G:C triad and effect of base mismatch/ionic strength on triplex stabilities.

Oligodeoxynucleotide (ODN) directed triplex formation has therapeutic importance and depends on Hoogsteen hydrogen bonds between a duplex DNA and a third DNA strand. T*A:T triplets are formed at neutral pH and C+*G:C are favoured at acidic pH. It is demonstrated that spermine conjugation at N4 of 5-Me-dC in ODNs 1-5 (sp-ODNs) imparts zwitterionic character, thus reducing the net negative charge of ODNs 1-5. sp-ODNs form triplexes with complementary 24mer duplex 8:9 show foremost stability at neutral pH 7.3 and decrease in stability towards lower pH, unlike the normal ODNs where optimal stability is found at an acidic pH 5.5. At pH 7.3, control ODNs 6 and 7 carrying dC or 5-Me-dC, respectively, do not show any triple helix formation. The stability order of triplex containing 5-Me-dC-N4-(spermine) with normal and mismatched duplex was found to be X*G:C approximately X*A:T > X*C:G > X*T:A. The hysteresis curve of sp-ODN triplex 3*8:9 indicated a better association with complementary duplex 8:9 as compared to unmodified ODN 6 in triplex 6*8:9. pH-dependent UV difference spectra suggest that N3 protonation is not a requirement for triplex formation by sp-ODN and interstrand interaction of conjugated spermine more than compensates for loss in stability due to absence of a single Hoogsteen hydrogen bond. These results may have importance in designing oligonucleotides for antigene applications.

Base Composition↗

Triplex formation at physiological pH by oligonucleotides incorporating 5-Me-dC-(N4-spermine).

Oligonucleotide (ODN) directed triplex formation has therapeutic importance and depends on Hoogsteen hydrogen bonds between a duplex DNA and a third strand. While T*A:T triplets are formed at neutral pH, C+*G:C are favoured at acidic pH. Herein it is shown that 18-mer ODN containing spermine conjugated to 5-Me-dC at N4 (1-5), form triplexes with complementary 24-mer duplex 8:9 at neutral pH (7.3, 100 mM NaCl). Under such conditions, control ODN's carrying dC (6) or 5-Me-dC (7) did not show any triple helix formation. Remarkably, the triplexes from spermine-conjugates (1-5) have foremost stability at neutral pH (7.1), unlike the behavior of normal ODN's where optimal stability is at acidic pH (5.5). These results have importance in designing oligonucleotides for antigene applications.

Base Sequence↗

Synthesis and evaluation of prolyl carbamate nucleic acids (PrCNA).

Carbamate linked prolyl nucleic acids are obtained in high yield and purity under mild conditions in solution and solid phase. p-Nitrophenylchloroformate is used as the activating reagent for alcohol. Homooligomers of PrCNA do not bind to DNA. The introduction of this modification in PNA sequences destabilizes the triplexes, inspite of enhancement in the base stacking.

Carbamates↗