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Biomedical subjects

R L Thomas

Publications and source records attributed to R L Thomas.

At least 55 records · Page 3Linked to original sources

Synthetic mucin fragments. Benzyl O-beta-D-galactopyranosyl-(1----3)-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----6)-2-acetamido-2-deoxy-alpha-D-galactopyranoside and O-alpha-L-fucopyranosyl-(1----3)-O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----6)-2-acetamido-2-deoxy-D-galactopyranose.

Benzyl 2-acetamido-6-O-(2-acetamido-2-deoxy-4,6-O-isopropylidene-beta-D- glucopyranosyl)-2-deoxy-3,4-O-isopropylidene-alpha-D-galactopyranoside (2) was obtained by acetalation of its parent disaccharide with 2,2-dimethoxypropane in hot N,N-dimethylformamide and in the presence of 4-toluenesulfonic acid. Glycosylation of 2 with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide (catalyzed by mercuric cyanide), followed by removal of the protecting groups afforded the title trisaccharide 7. A second product was also isolated, which was identified as a derivative of 7 having a 2-cyanopropyl group. Glycosylation of diacetal 2 with 2,3,4-tri-O-benzyl-alpha-L-fucopyranosyl bromide (under catalysis by bromide ion), followed by systematic removal of the protecting groups furnished the title trisaccharide 13. The structures of both 7 and 13 were established by 13C-n.m.r. spectroscopy.

Magnetic Resonance Spectroscopy↗

Triploid fetus: an important consideration in the evaluation of very high maternal serum alpha-fetoprotein.

Two patients referred for evaluation of very high maternal serum alpha-fetoprotein (10-20 multiples of the median) were carrying triploid fetuses with placentas showing features of partial hydatidiform mole. The diagnosis of fetal triploidy should be considered when there is a very high maternal serum alpha-fetoprotein and no ultrasound evidence of open neural tube defect, ventral wall defect, or any other explanation. Therefore, chromosomal analysis of amniotic fluid cells in such cases is essential.

Amniotic Fluid↗

Preterm and term fetal cardiac and movement responses to vibratory acoustic stimulation.

To assess fetal response to vibratory acoustic stimulation, 24 preterm (group A; less than 36 weeks' gestation) and 30 term (group B; greater than or equal to 36 weeks' gestation) pregnancies were studied. Study variables were perceived fetal movement, fetal heart rate, and fetal heart rate pattern. Observer- and patient-perceived fetal movement responses were noted in most cases but were slightly more common in term patients (group A: + fetal movement, patient 87.5%/observer 87.5%) group B: + fetal movement, patient 96.7%/observer 90%). Baseline changes in fetal heart rate (greater than or equal to 10 beats/min) were observed in 46% of preterm fetuses and 70% of term fetuses. Tachycardia (fetal heart rate greater than 160 beats/min) was a common finding in both groups. In group A, tachycardia after vibratory acoustic stimulation persisted more than 1 minute in 29.2% and more than 5 minutes in 12.5% of patients. In group B tachycardia beyond 1 and 5 minutes was noted in 73.3% and 50% of patients, respectively. A significant shift to "awake" fetal heart rate patterns occurred in both groups; 29% to 79% was noted in group A (p less than 0.001) and 46.7% to 90% in group B (p less than 0.001). When vibratory acoustic stimulation was used, the high occurrence of increased baseline, tachycardia, and emergence of unusual fetal heart rate patterns must be recognized to adequately interpret fetal heart rate tracings.

Acoustic Stimulation↗

Metastatic bone marrow involvement from supraglottic squamous cell carcinoma.

A case of an aggressive supraglottic squamous cell carcinoma, which was managed with neo-adjuvant chemotherapy and radical surgery, is described. The post-operative course was of rapid deterioration and death due to progressive metastatic disease involving bone marrow and liver. This is the first reported case of bone marrow infiltration by squamous cell carcinoma of the head and neck diagnosed ante-mortem. The incidence and pattern of metastatic disease from head and neck tumours is reviewed, and the importance of initial staging in determining the risk of distant metastatic disease is emphasised.

Bone Marrow↗

Pregnancy complicated by hemipelvectomy: case presentations and review of the literature.

Nine patients with posthemipelvectomy with subsequent delivery of 13 living children are reported in the world's literature. This radical procedure is possible only in a modern age of intensive medical and surgical support. Additional cases can be expected in the future. We present two additional patients and three children to be added to the existing experience and also provide a review of obstetric and gynecologic considerations in the care of these unusual patients.

Adult↗

Synthesis of uridine 5'-(2-acetamido-2,4-dideoxy-4-fluoro-alpha-D-galactopyranosyl) diphosphate and uridine 5'-(2-acetamido-2,6-dideoxy-6-fluoro-alpha-D-glucopyranosyl) diphosphate.

Benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranoside was converted into its 4-O-(methylsulfonyl) derivative (2) by treatment with methanesulfonyl chloride in pyridine. Displacement of the methylsulfonyloxy group of 2 with fluoride ion afforded benzyl 2-acetamido-3,6-di-O-benzyl-2,4-dideoxy-4-fluoro-alpha-D-galactopyranosi de, which on hydrogenolysis, followed by acetylation, furnished 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-fluoro-D-galactopyranose. Treatment of this and of 2-acetamido-1,3,4-tri-O-acetyl-2,6-dideoxy-6-fluoro-D-glucopyranose with trimethylsilyl trifluoromethanesulfonate in 1,2-dichloroethane at approximately 50 degrees afforded the 4-deoxy-4-fluoro- or the 6-deoxy-6-fluoro-oxazolines (5) and (11), respectively. Reaction of 5 and 11 with dibenzyl phosphate in 1,2-dichloroethane produced the alpha-linked dibenzyl phosphate derivatives 6 and 12, respectively. Catalytic hydrogenation of 6 provided 2-acetamido-3,6-di-O-acetyl-2,4-dideoxy-4-fluoro-alpha-D-galactopyranosy l phosphate (7), and that of 12 gave 2-acetamido-3,4-di-O-acetyl-2,6-dideoxy-6-fluoro-alpha-D-glucopyranosyl phosphate (13). Coupling of 7 and 13 with uridine 5'-monophosphomorpholidate in dry pyridine at approximately 37 degrees, followed by O-deacetylation, furnished the title compounds, respectively, isolated and characterized as their respective dilithium salts.

Carbohydrate Conformation↗

Synthetic mucin fragments. Benzyl O-(2-acetamido-2-deoxy-alpha-D-glucopyranosyl)-(1----3)-O-beta-D- galactopyranosyl-(1----3)-O-[(2-acetamido-2-deoxy-beta-D-glucopyran osy l)- (1----6)]-2-acetamido-2-deoxy-alpha-D-galactopyranoside and benzyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-O-beta-D- galactopyranosyl-(1----3)-O-[beta-D-galactopyranosyl-(1----6)]-2-ac eta mido- 2-deoxy-alpha-D-galactopyranoside.

Treatment of benzyl 2-acetamido-2-deoxy-alpha-D-galactopyranoside with 4-methoxybenzaldehyde dimethyl acetal in N,N-dimethylformamide in the presence of 4-toluenesulfonic acid afforded the 4,6-O-(4-methoxybenzylidene) acetal, which was glycosylated with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide (1). Reductive ring-opening of the acetal group provided a 6-O-(4-methoxybenzyl) derivative (4) which was glycosylated with 1, followed by removal of the 4-methoxybenzyl ether group, to give benzyl 2-acetamido-2-deoxy-3,4-di-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyran osyl)- alpha-D-galactopyranoside (7). The disaccharide diol 5, obtained from 4, and benzyl O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl-(1----3) -O- (2,4,6-tri-O-acetyl-beta-D-galactopyranosyl)-(1----3)-2-acetamido-2-deox y- alpha-D-galactopyranoside (11) were similarly glycosylated with 1 to afford a trisaccharide derivative 9 and a tetrasaccharide derivative 14, respectively. Diol 11 was also condensed with 2-methyl-(3,4,6-tri-O-acetyl-1,2-di-deoxy-alpha-D-glucopyrano)-[2, 1-d]-2- oxazoline to give a tetrasaccharide derivative 16. O-Deacetylation of trisaccharides 7 and 9, and tetrasaccharides 14 and 16 furnished trisaccharides 8 and 10, and the title tetrasaccharides 15 and 17, respectively. The structures of compounds 8, 10, 15, and 17 were established by 13C-n.m.r. spectroscopy.

Carbohydrate Conformation↗

Rapid estimation of unbound lidocaine clearance in cardiac patients: implications for reducing toxicity.

The clearance (CL), volume of distribution (Vd) and elimination half-life (t1/2), based on unbound and total concentration-time data, were estimated using two serum lidocaine concentrations drawn approximately 6 and 12 hours after the initiation of continuous intravenous lidocaine therapy in nine patients with myocardial infarction (MI) (in the immediate postinfarct period) and in 12 patients with ventricular arrhythmias. No significant intergroup differences were found for any of the parameters based on unbound or total lidocaine concentration-time data. A significant (P less than .01) correlation was found between measured unbound lidocaine and unbound lidocaine concentrations predicted using alpha-1-acid glycoprotein (AAGP) and total serum lidocaine concentrations. However, the predicted values were significantly lower than the measured values for both groups (P less than .001). Significant correlations were found between total and unbound volumes of distribution and between total and unbound clearances. Coefficients of determination (r2) for these correlations were 0.6906 and 0.9178 respectively. The relationship between total and unbound clearance allows rapid estimation of unbound clearance from two total serum lidocaine concentrations. Unbound clearance can then be used to determine patient-specific maximum infusion rates and reduce the risk of central nervous system toxicity from lidocaine.

Adult↗

Synthesis of O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-O-beta-D- galactopyranosyl-(1----4)-2-acetamido-2-deoxy-D-glucopyranose and two related trisaccharides containing the "lacto-N-biose II" unit.

Condensation of 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D- glucopyranosyl)-2,4,6-tri-O-acetyl-alpha-D-galactopyranosyl bromide (1) with benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranoside in boiling benzene and in the presence of mercuric cyanide afforded a trisaccharide that was O-deacetylated to give benzyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1----3)-O-beta-D- galactopyranosyl-(1----4)-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranosid e, the benzyl groups of which were cleaved by catalytic hydrogenolysis to furnish the title trisaccharide. Alternatively, bromide 1 was allowed to react with 2-acetamido-1,6-anhydro-3-O-benzyl-2-deoxy-beta-D-glucopyranose in 1:1 benzene-nitromethane in the presence of mercuric cyanide, followed by O-deacetylation, column chromatography, and reacetylation to give O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D- glucopyranosyl)-(1----3)-O-(2,4,6-tri-O-acetyl-beta-D-galactopyranosyl)- (1----4)-2-acetamido-1,6-anhydro-3-O-benzyl-2-deoxy-beta-D-glucopyranose . Acetolysis, followed by catalytic hydrogenation and subsequent O-deacetylation furnished the title trisaccharide. A similar condensation of bromide 1 with 4-nitrophenyl 2-acetamido-2-deoxy-4,6-O-(4-methoxybenzylidene)-beta-D-glucopyran oside and 2-nitrophenyl 2-acetamido-2-deoxy-4,6-O-(4-methoxybenzylidene)-alpha-D-galactopy ranoside produced two trisaccharide derivatives, the acetal groups of which were cleaved in hot, 60% aqueous acetic acid, and the resulting diol intermediates O-deacetylated to furnish the desired trisaccharides 4-nitrophenyl O-(2-acetamido-2-deoxy-beta-D- glucopyranosyl)-(1----3)-O-beta-D-galactopyranosyl)-(1----3)-2-acetamido -2- deoxy-beta-D-glucopyranoside and 2-nitrophenyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1----3)-O-beta- D-galactopyranosyl-(1----3)-2-acetamido-2-deoxy-beta-D-galactopyranoside .

Carbohydrate Conformation↗

Review of intermittent dobutamine infusions for congestive cardiomyopathy.

Dobutamine is a potent inotropic agent traditionally used for treatment of acute cardiac decompensation of congestive heart failure (CHF). It acts primarily by increasing myocardial contractility and cardiac output. It has a rapid onset of action, a half-life of 2 minutes, and a duration of action of 10 minutes. Recently, the therapeutic effect of dobutamine was noted to be prolonged beyond the discontinuation of an infusion, persisting for 4-10 weeks after infusion of 48-72 hours. Because of this prolonged effect, dobutamine infusions were evaluated in outpatients with intractable CHF and were effective in improving their functional status. No effect on survival rates may be expected, but this form of therapy may improve the patient's lifestyle. Although several factors may limit the application of dobutamine infusion to outpatients, it offers an effective alternative to traditional therapy for select patients.

Dobutamine↗

Prepartum diagnosis of limb-shortening defects with associated hydramnios.

Two cases of skeletal dysplasia with limb-shortening abnormalities are presented. In association with the skeletal abnormalities, gross hydramnios was noted. A review of the existing literature reveals that coexistent fetal skeletal dysplasia and hydramnios have an extremely poor prognosis, especially in the nonachondroplastic patient with singleton fetus. The two cases presented here and the accompanying review emphasize the importance of recognizing this association in providing appropriate counseling to parents.

Adult↗

Encainide: a new antiarrhythmic agent.

Encainide is classified as a type Ic antiarrhythmic agent. Absorption is essentially complete, but bioavailability is variable because of first-pass metabolism. Two metabolic phenotypes, extensive and poor metabolizers, have been identified. O-demethyl encainide and 3-methoxy-O-demethyl encainide are active metabolites of encainide and contribute significantly to its antiarrhythmic effect. In clinical trials, encainide has been shown to be highly effective in suppressing premature ventricular contractions and ventricular tachyarrhythmias. The drug is useful in treating ventricular arrhythmias refractory to other agents. Encainide is also moderately effective in supraventricular arrhythmias involving an accessory pathway. It is highly effective in cases of Wolff-Parkinson-White syndrome, where the accessory pathway has a short refractory period. Common adverse effects of encainide are dizziness, visual disturbances, nausea, and headache. Encainide appears to be a safe and effective antiarrhythmic agent with few adverse effects and negligible hemodynamic effects. Encainide may be a useful agent for ventricular and supraventricular arrhythmias, particularly those refractory to other agents.

Anilides↗

Emotional mood states and retrieval in episodic memory.

The effect of an experimentally induced depressed mood state on recall of target words embedded in sentences was examined. The objective was to determine if the induction of a depressed mood can affect output or retrieval from episodic memory. The experimental sequence was as follows: All subjects studied a list of either elaborated or base sentences, rating them for complexity, in an incidental retention paradigm; this was followed by the induction of a depressed or neutral (control) mood, using a standard and a short form of the Velten mood induction procedure; finally, subjects were given an unanticipated cued recall test of the target adjectives. In all tests, subjects showed a reduction in recall owing to the depressed mood, which provided evidence for retrieval effects of the mood state. Elaboration led to superior recall of target items, and there was no effect of delayed recall. The results are briefly discussed within the framework of a resource allocation theory.

Cues↗

Emotional mood states and memory: elaborative encoding, semantic processing, and cognitive effort.

The effects of experimentally induced mood states on recall of target words embedded in sentences or alone were examined in three experiments. All experiments focused on the role of a depressed-mood induction on recall and looked at the effects of elaborative encoding, semantic processing, or cognitive effort. The overall effect of the depressed-mood state was to reduce recall in all three situations; however, the opportunity to process information semantically still led to superior recall in the depressed condition. In contrast, the superiority of recall of high-effort items disappeared in the depressed condition, suggesting that subjects may differentially allocate resources when under a depressed-mood state. The results are briefly discussed within the framework of a resource allocation theory.

Affect↗