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Biomedical subjects

R Pillai

Publications and source records attributed to R Pillai.

At least 55 records · Page 3Linked to original sources
PubMed1996

Fate of the native aorta after repair of acute type A dissection: a magnetic resonance imaging study.

OBJECTIVE: To determine late patency of the aortic false lumen and propensity for aneurysm formation after repair of type A dissection. DESIGN: Retrospective follow up study. SETTING: Regional cardiac surgical unit. PATIENTS: 28 patients after repair of type A dissection. METHODS: Magnetic resonance imaging (MRI) was performed between 6 weeks and 12 months after operation. RESULTS: A patent distal false lumen with demonstrable blood flow was found in 22 patients (78%). Only six patients had complete obliteration of the false lumen by thrombus. The conduct of operation did not influence this. Nine patients (32%) showed aneurysmal dilatation of the false lumen and three had a repeat operation. CONCLUSIONS: So-called "successful repair" of aortic dissection does not obliterate the distal false lumen. MRI is a safe and effective radiological procedure for determining patency and dilatation in the false lumen. Patients with type A dissection with blood flow in the false lumen should be studied every 6 months to look for aneurysmal dilatation.

Acute Disease↗
PubMed1995

Myxoma of the aortic valve.

Myxomas are one of the most common cardiac tumors but usually are confined to the atria. Although described in all cardiac chambers and on all cardiac valves, only one postmortem case of an aortic valve myxoma has been published. We present the case of a young man with an aortic valve myxoma with peripheral embolization. The other pathologic conditions with which valvular myxomas can be confused are compared and discussed.

Adult↗
PubMed1995

Comparison of implantation techniques using freestyle stentless porcine aortic valve.

Stentless porcine aortic valves demonstrate superior hemodynamic performance when compared with their stented counterparts. The technical considerations for implanting these valves can be demanding. The Medtronic Freestyle aortic root bioprosthesis resembles an allograft, has zero-pressure-fixed leaflets treated with an antimineralization agent, and can be implanted using a variety of techniques. In this study of that valve, total root replacement (TRR) was compared with a partial scallop aortic inclusion technique (PSI). Implications were performed in 75 patients (49 PSI and 26 TRR). There were no significant differences with respect to age, sex, or incidence of concomitant procedures. Mean aortic cross-clamp times were significantly less in the PSI group than in the TRR group (51.8 +/- 11.7 minutes versus 125.5 +/- 19.7 minutes; p = 0.0001). At discharge, mean systolic gradients seen on color-flow Doppler echocardiography were less in the TRR group than in the PSI group (6.17 +/- 3.66 versus 10.01 +/- 4.83 mm Hg; p = 0.014). Discharge echocardiography revealed trivial valve regurgitation in 8.3% of the TRR group and in 41.7% of the PSI group (p = 0.004). No patient experienced any significant valvular regurgitation on discharge echocardiography. We conclude that early experience with the Medtronic Freestyle aortic root bioprosthesis shows excellent short-term function regardless of implantation technique. Shorter cross-clamp times, comparable with those of stented valve procedures, occurred with PSI implantation. We anticipate that effects on long-term durability will be beneficial.

Adult↗
PubMed1995

Aortic valve replacement with the freestyle stentless xenograft.

We performed aortic valve replacement with the Free-style stentless xenograft in 55 consecutive patients requiring a bioprosthesis. Thirty-four were male and 21 female, and all were in New York Heart Association class III to V. Ages ranged from 44 to 87 years (median, 74 years). Fifteen patients required coronary bypass grafts. One required mitral valve replacement (after attempted repair) and another needed repair of both the mitral and tricuspid valves. Four were reoperations. Implantation involved two-thirds transection at the aortic sinotubular junction and insertion of the xenograft cylinder into the aortic sinuses. Ischemic times ranged from 34 to 58 minutes for isolated aortic valve replacement and up to 79 minutes for aortic plus mitral valve replacement. Two patients died in the hospital of left ventricular failure. Survivors underwent echocardiographic assessment of systolic gradients. The mean gradients for valve sizes of 21, 23, 25, and 27 cm were 13, 10, 8, and 6.5 mm Hg, respectively. No patient had more than trivial regurgitation. One died late of left ventricular failure. The Free-style stentless xenograft is user friendly and can be employed in a calcified root. The "cylinder within a cylinder" method is simple and reproducible and avoids aortic regurgitation. Follow-up has shown excellent hemodynamic function and decreasing gradients.

Adult↗
PubMed1995

Time-related hemodynamic changes after aortic replacement with the freestyle stentless xenograft.

BACKGROUND: The Freestyle valve is a porcine aortic root fixed with net zero pressure across the cusps and treated with the anticalcification agent alpha-aminooleic acid. We evaluated the hemodynamic function of this stentless valve. METHODS: We implanted the valve into 80 consecutive patients scheduled to receive a bioprosthesis. Sixty-nine patients were more than 70 years old and 14 had calcified aortic sinuses. The "cylinder within a cylinder" implantation technique was used. Twenty-seven patients received coronary grafts, and 3 had mitral repair. All patients were studied echocardiographically during week 1 and 41 were studied at 6 months. RESULTS: Median ischemic time for isolated aortic valve replacement was 44 minutes. There were four hospital deaths, none valve related. No patient had more than trivial aortic regurgitation. Mean systolic gradients for valve sizes 21 to 25 mm fell significantly with time (p < or = 0.05) due to remodeling of the porcine root and early regression of left ventricular hypertrophy. Late hemodynamic function was equivalent to an aortic homograft. CONCLUSIONS: The Freestyle valve is easily implanted and has excellent hemodynamics. Transvalvular gradients decrease progressively.

Adult↗
PubMed1995

Estrone sulfate analogs as estrone sulfatase inhibitors.

The high serum concentration of estrone sulfate and the presence of estrone sulfatase in breast tumors constitute an important mechanism of local synthesis of estrogens in the tissue. Thus, inhibitors of estrone sulfatase may be effective in the treatment of estrogen-dependent breast cancer. In this study, we synthesized several isostructural analogs of estrone sulfate (estrone-3-methylsulfonate, estrone phosphate, 3-desoxyestradiol-3-methylenesulfonate, and 3-desoxyestrone-3-methylenesulfonate) and tested them on human placental sterylsulfatase. The results were (i) The Ki of 3-desoxyestrone-3-methylenesulfonate 12 and 3-desoxyestradiol-3-methylenesulfonate 7 are more than 100-fold higher than the Ki or KM values for estrone sulfate, (ii) As compared to estrone sulfate, the Ki value for estrone-3-methylsulfonate 2 is about 30-fold higher, while estrone phosphate 3 is bound by the sulfatase with roughly the same affinity as estrone sulfate. The results shed some light on the electronical and sterical requirements for high affinity binding to the enzyme.

Binding Sites↗
PubMed1995

Impaired platelet aggregation after cardiopulmonary bypass in man: enhancement of collagen-induced aggregation in whole blood and plasma by adrenaline ex vivo.

1. We tested the effect of intravenous adrenaline at 0.55-1.10 nmol min-1 kg-1 (for 3-8 min, at 7-10 min post bypass; n = 7) on both microaggregation in hirudinized whole blood, using platelet counting, and macroaggregation in platelet-rich plasma, using optical aggregometry. Control (n = 12) blood samples were taken before and at 10 and 20 min after bypass. 2. Post-bypass plasma adrenaline levels (nmol/l) increased slightly in controls (1.0 versus 0.7 at 10 min, medians; P = 0.05) and markedly with adrenaline infusion (36 versus 0.5 before infusion, P = 0.02). Microaggregation (percentage decrease in single platelets) in stirred blood, reflecting largely ADP-dependent 'spontaneous' aggregation, was not influenced by adrenaline infusion. In contrast, collagen (0.2 microgram/ml)-induced microaggregation in blood was enhanced by adrenaline (92% versus 41%, P = 0.02), with no change in controls (60% versus 53%, P = 0.61). 3. In controls, collagen (0.6 microgram/ml)-induced macroaggregation in platelet-rich plasma (extent of increase in light transmission, cm) was impaired at 10 min post bypass (5.3 versus 12.1 before bypass, P = 0.01), but was enhanced by adrenaline (7.0 versus 3.6 before infusion, P = 0.02). Platelet counts (x 10(9)/l) were decreased postbypass (155 versus 220, P = 0.02) and were not influenced by adrenaline infusion (167, P = 0.93).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Mutational mapping of kinetic and pharmacological properties of a human cardiac cAMP phosphodiesterase.

We have created a series of deletion mutants of a human cardiac cAMP phosphodiesterase in order to define sequences necessary for function and to identify residues required for inhibition by cGMP and by the drugs milrinone and trequinsin. These truncated constructs were expressed in yeast cells, and their biochemical properties were analyzed. The mutations define an amino acid sequence that is essential for function. Among the active constructs, there was considerable variability in the level of expression and in the stability of the proteins, with the full-length and near full-length constructs being the least stable. There were, however, no significant changes in Km values among the active enzymes. Cation studies confirmed that Mn2+ is a more efficient cofactor than Mg2+ or Co2+. Interestingly, Mn2+ acts as a more efficient cofactor for cGMP inhibition as well. Although IC50 values for the drugs trequinsin and milrinone were not significantly altered by deletions, there was a decrease in cGMP IC50 values for the smaller constructs, indicating a role for amino acid residues outside the catalytic region in cGMP inhibition. We also demonstrate in vivo inhibition of this enzyme in yeast cells grown in the presence of pharmacological inhibitors, allowing for the selection of drug-resistant mutants. Finally, we have constructed and analyzed chimeric genes in which portions of this phosphodiesterase are replaced with homologous sequences from a closely related phosphodiesterase isozyme that is expressed in brain. Our results demonstrate that sequence variations between related isozymes account for more than just pharmacological distinctions and may reflect significant structural differences.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1994

Cloning of a rat cDNA encoding dihydroxypolyprenylbenzoate methyltransferase by functional complementation of a Saccharomyces cerevisiae mutant deficient in ubiquinone biosynthesis.

3,4-Dihydroxy-5-hexaprenylbenzoate methyltransferase (DHHB-MTase) is the product of the COQ3 gene in Saccharomyces cerevisiae and catalyses the fourth step in the biosynthesis of ubiquinone (coenzyme Q) from p-hydroxybenzoic acid. A full-length cDNA encoding a mammalian homologue of DHHB-MTase was isolated from a newly constructed rat testis cDNA library by functional complementation of a coq3 deletion mutant of S. cerevisiae. The complementing clone contained a 1.1-kb poly(A)(+)-tailed insert with a 858-bp open reading frame and presumably encodes 3,4-dihydroxy-5-polyprenylbenzoate-MTase. The deduced rat amino acid (aa) sequence has a 39% identity over 138 aa with the yeast DHHB-MTase and a 37% identity over this same region with an Escherichia coli protein encoded by the ubiG gene, a MTase that catalyses the terminal step of ubiquinone biosynthesis. The rescue of the yeast coq3 mutant by the rat homologue suggests that yeast and rat synthesize ubiquinone via the same early steps in this pathway.

Amino Acid Sequence↗
PubMed1994

Topical aprotinin in cardiac operations.

We performed a prospective, randomized, double-blind trial of topical aprotinin versus placebo in 100 patients undergoing cardiac operations with cardiopulmonary bypass. Fifty-five patients received aprotinin. Forty underwent coronary artery bypass grafting (CABG) and 15 valve replacement +/- CABG. Of 45 patients in the control group 38 underwent CABG and 7 valve replacement +/- CABG. Aprotinin (50 mL; 70 mg) or placebo was applied topically to the heart, pericardium, and mediastinum before sternal closure. There were five reentries for bleeding with a surgical site identified in four. Mean blood loss was significantly less in the aprotinin group (653 versus 903 mL; p = 0.002), and fewer aprotinin patients received blood as a volume expander (67.5% versus 88%; p = 0.03). In coronary patients alone when aspirin administration was continued until the day of operation there was no difference between treatment and placebo groups (768 versus 879 mL). When aspirin administration was discontinued 2 weeks before operation there was a significant difference (558 versus 884 mL; p = 0.016) as in the group overall. This provides the potential for intrapericardial instillation for patients with excessive postoperative bleeding.

Administration, Topical↗
PubMed1994

Inhibition of human placental sterylsulfatase by synthetic analogs of estrone sulfate.

Synthetic analogs of estrone sulfate which carry differently substituted sulfonyl groups at position 3 of an invariable 3-desoxyestrone (dE1) moiety were tested in vitro as inhibitors of the human placental sterylsulfatase. Using both placental microsomes and a highly purified placental sterylsulfatase preparation as the enzyme source and dehydroepiandrosterone [35S]sulfate or estrone [35S]sulfate as the substrate, the following order of inhibitory potencies was observed: dE1-3-sulfonylchloride > dE1-3-sulfonylfluoride approximately dE1-3-sulfonate > dE1-3-sulfonamide approximately 3-methylsulfonyl-dE1. According to the results, the association of enzyme and inhibitor appears to be favored by an electronegative substituent at the sulfur atom (-C1, -F, -O-). Since, however, even the most potent synthetic inhibitor was bound by the enzyme with significantly lower affinity than was the natural substrate estrone sulfate, an oxygen function between the aromatic ring and the sulfur atom may be necessary for high affinity binding towards the sterylsulfatase. In addition to its fast reversible association with the enzyme, dE1-3-sulfonylchloride further affected the sulfatase activity in a time-dependent manner. This latter inhibitory activity which may be due to a covalent modification (alkylation) of sterylsulfatase by the analog was partially prevented in the presence of substrate.

Arylsulfatases↗
PubMed1994

Aprotinin and bleeding in profoundly hypothermic perfusion.

Clinical observation led us to believe that aprotinin fails to preserve haemostatic function in patients undergoing deep hypothermic perfusion with or without circulatory arrest. A retrospective study was made of blood loss in 80 consecutive acute Type A dissection patients before and during the aprotinin era (1987-1992). After 1988 all patients were cooled below 20 degrees C pending circulatory arrest. Fourteen patients underwent aortic root replacement and 66 replacements of the ascending aorta. Age distribution (range 22-79 years) and type of operation were similar in the aprotinin and control groups. The impervious Hemashield (Meadox) graft was used for all but five patients. These underwent aortic root replacement with preclotted, valved conduits. Overall the mean blood loss for 27 patients operated without aprotinin was 837 ml per 24 h (standard error +/- 90) and for 53 patients with aprotinin 1,929 ml per 24 h (standard error +/- 90). There was a significant difference between the two groups when profoundly hypothermic perfusion was used, with greater bleeding in aprotinin-treated patients. There were six re-entries in the aprotinin group and none in the control patients. There were ten hospital deaths (11.1%). A greater incidence of bleeding and thrombosis-related deaths was recorded for the aprotinin-treated patients. In addition, four surviving aprotinin patients suffered severe coagulation defect with blood loss greater than 4,500 ml and platelets less than 50 x 10(6). We suggest that aprotinin inhibits the protease enzymes which maintain the fluid state of blood during hypothermic low flow and arrest states. Disseminated intravascular coagulation may consume platelets thereby predisposing to abnormal bleeding and potentially fatal thrombotic events. The use of aprotinin in profoundly hypothermic perfusion should be adopted cautiously.

Adult↗
PubMed1994

Macroaggregation of platelets in plasma, as distinct from microaggregation in whole blood (and plasma), as determined using optical aggregometry and platelet counting respectively, is specifically impaired following cardiopulmonary bypass in man.

We determined changes in platelet aggregability following cardiopulmonary bypass, using optical aggregometry to assess macroaggregation in platelet-rich plasma (PRP), and platelet counting to assess microaggregation both in whole blood and PRP. Hirudin was used as the anticoagulant to maintain normocalcaemia. Microaggregation (%, median and interquartile range) in blood stirred with collagen (0.6 micrograms/ml) was only marginally impaired following bypass (91 [88, 93] at 10 min postbypass v 95 (92, 96] prebypass; n = 22), whereas macroaggregation (amplitude of response; cm) in PRP stirred with collagen (1.0 micrograms/ml) was markedly impaired (9.5 [8.0, 10.8], n = 41 v 13.4 [12.7, 14.3], n = 10; p < 0.0001). However, in PRP, despite impairment of macroaggregation (9.1 [8.5, 10.1], n = 12), microaggregation was near-maximal (93 [91, 94]), as in whole blood stirred with collagen. In contrast, in aspirin-treated patients (n = 14), both collagen-induced microaggregation in whole blood (49 [47, 52]) and macroaggregation in PRP (5.1 [3.8, 6.6]) were more markedly impaired, compared with control (both p < 0.001). Similarly, in PRP, macroaggregation with ristocetin (1.5 mg/ml) was also impaired following bypass (9.4 [7.2, 10.7], n = 38 v 12.4 [10.0, 13.4]; p < 0.0002, n = 20), but as found with collagen, despite impairment of macroaggregation (7.2 [3.5, 10.9], n = 12), microaggregation was again near-maximal (96 [93, 97]). The response to ristocetin was more markedly impared after bypass in succinylated gelatin (Gelofusine) treated patients (5.6 [2.8, 8.6], n = 17; p < 0.005 v control), whereas the response to collagen was little different (9.3 v 9.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗
PubMed1994

An audit of cardiac surgery in patients aged over 70 years.

With an increasingly aged population, the number of patients requiring treatment for cardiovascular diseases will rise. Previous expectations of cardiac surgery in the over-seventies have been poor, with surgery being very much a last resort. We decided to test whether this was appropriate, and to determine whether the priority of surgery affected the outcome. Three hundred and six patients over the age of 70 were operated on in our unit in a 4 1/2-year period, 210 as elective operations and 96 as emergencies. Eighty-nine per cent were in NYHA class III-IV pre-operatively and half had other significant medical problems. Most (46%) underwent coronary artery surgery. The methods used were identical to those used for the younger patients in both operative approach and post-operative management. The overall mortality was 6.9%; 1.9% for elective procedures and 16.7% for emergencies (12.3% when catastrophic pathologies are excluded). However, the morbidity was not significantly different between the two groups and the length of post-operative ventilation and hospital stay were likewise not significantly different. Follow-up of the survivors showed no late deaths, and 87% were in NYHA class I and II. Of the others, 25 have required additional hospital admissions for associated cardiac problems. One required another invasive procedure (a PTCA), but none has required further surgery. The findings of low mortality for elective cardiac surgery in this age group are in agreement with other reports. If early referral prevents emergency surgery, it should be avidly pursued, in view of the improved outcome for elective surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Use of a yeast expression system for the isolation and analysis of drug-resistant mutants of a mammalian phosphodiesterase.

Saccharomyces cerevisiae strain PP5 has a phosphodiesterase (PDE) deficiency that results in heat-shock sensitivity due to the intracellular accumulation of cAMP. This strain also carries the cam mutation, which confers permeability to cAMP and, as shown here, to other compounds. Expression of rat type IV PDE in these cells caused them to revert to heat-shock resistance. Treatment of the transformed PP5 cells with rolipram, an antidepressant in humans and a potent inhibitor of type IV PDEs, reinstated sensitivity to heat shock. The biochemical properties of deletion mutants of this PDE were determined, and an active enzyme of minimum length was created. Reversion to heat-shock resistance was then used to select for PDE mutants refractory to the inhibitory effects of rolipram. Four mutants (A1, A2, A3, and A5) were isolated. Each carries a single point mutation; two have mutations in the same codon. Each mutant showed distinct properties, based on analysis of their substrate kinetics and IC50 values for a variety of inhibitors. Mutant A5 had a reduced activity for substrate, mutants A1 and A3 showed no change in substrate kinetics, and mutant A2 displayed an increase in activity. For most mutants, the drug resistance was confined to the class of drug used in the selection. This study shows that it is possible to recreate in yeast cells the susceptibility of mammalian enzymes to pharmacological agents. Our study also demonstrates that such systems can be used to select rare mutants useful in the analysis of drug-protein interactions.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Argyrophilic nucleolar organizer regions (AgNORs) in inflammatory pre-malignant and malignant lesions of the uterine cervix.

Nuclear organizer regions (NORs) code for ribosomal RNA and are associated with non-histone nucleoproteins, which can be identified by silver staining (AgNORs). AgNORs have been correlated to proliferative activity of tumors and hence may be prognosis-related. The present study evaluates AgNOR counts in inflammatory lesions of the uterine cervix, cervical intra-epithelial neoplasia, and invasive cervical squamous carcinoma. Significant variation in AgNOR counts were observed between the three study groups, with invasive carcinoma showing maximum counts. Further, a highly significant positive correlation was observed between AgNOR counts and tumor progression. These results therefore suggest that AgNOR counts may be of significance in the evaluation of cervical carcinogenesis and could elaborate histopathological diagnosis of cervical lesions.

Carcinoma, Squamous Cell↗