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Biomedical subjects

R A Watson

Publications and source records attributed to R A Watson.

At least 37 records · Page 2Linked to original sources

Placement of metallic stents in ureters obstructed by carcinoma of the cervix to maintain renal function in patients undergoing long-term chemotherapy.

OBJECTIVE: Metallic stents, sometimes augmented by "J" endostents, were placed in ureters obstructed by advanced carcinoma of the cervix to improve or maintain renal function in these patients at a level necessary to pursue long-term chemotherapy and radiation therapy. SUBJECTS AND METHODS: Seventeen ureters in 11 patients were treated with metallic stents, which were placed by an anterograde approach in 10 patients and by a retrograde approach in one. An anterograde ureteroneocystostomy was necessary in two of the 11 patients. J endostents were placed for I month in all patients. In 10 ureters, J endostents were reintroduced during follow-up 1-48 months later. RESULTS: In 17 ureters, metallic stents were successfully placed; in the remaining three ureters, the procedures were aborted because of technical difficulties. The goal of improving and maintaining renal function was met in 10 patients. Serum creatinine levels returned to normal in four patients and stabilized at a range of 2.7-3.2 mg/dl in six more patients, permitting treatment with chemotherapy, radiation therapy, or both. Four of the 11 patients died within 4 months after treatment, and three more died within 2 years. At the time of death or last follow-up, seven metallic stents and eight combinations of metallic stents and J endostents were patent. Complications were minor. CONCLUSION: Placement of metallic stents is recommended as an effective method to ensure patency and to facilitate cystoscopic replacement of J endostents in ureters compromised by carcinoma of the cervix. Renal function can be maintained, allowing chemotherapy. Survival is governed by the effectiveness of chemotherapy and radiation therapy.

Adult↗

Incidence of stool guaiac conversion following extracorporeal shock wave lithotripsy.

OBJECTIVES: To study, in a prospective fashion, acute traumatic effects on the gastrointestinal tract of patients treated by extracorporeal shock wave lithotripsy (ESWL). METHODS: Stool samples from each of 54 patients were tested before and after ESWL for conversion to hemoccult positive. A minimum of one negative pre-ESWL stool guaiac test was required for inclusion into the study. A minimum of two stool guaiac tests were done after ESWL to verify negativity. Patients who converted to a positive hemoccult test after ESWL were then evaluated by colonoscopy for the source of bleeding. RESULTS: Fifty patients completed the study. A single patient (2.0%) converted to a positive post-ESWL hemoccult test and was evaluated with colonoscopy. This patient was found to have two benign adenomatous polyps in the sigmoid and descending colon after treatment for a left renal pelvis calculus. An additional patient with a slightly positive post-ESWL conversion refused further evaluation. The overall post-ESWL conversion rate to guaiac positive, therefore, was less than 4% (2 of 51 patients). CONCLUSIONS: There is no evidence of significant trauma or detectable bleeding in the normal gastrointestinal tract caused by ESWL as measured by postprocedure stool guaiac testing. Guaiac testing of the stool after ESWL may unmask pre-existing gastrointestinal disease. Therefore a positive guaiac test after ESWL warrants further evaluation. This study reaffirms that ESWL is a safe, minimally invasive technique for the treatment of urolithiasis, without significant adverse side effects on the gastrointestinal tract.

Digestive System↗

Use of nasal peak flow to assess nasal patency.

Nasal patency is usually assessed in the laboratory by measuring nasal airflow conductance (Gnaw); peak inspiratory and/or expiratory flow measurements via the nose (PIFna, PEFna) have been proposed as simple alternatives suitable for home monitoring of rhinitis. We have compared the scale of changes in PIFna and PEFna (measured with a pneumotachograph) with changes in Gnaw (measured by the forced-oscillation technique) when nasal patency was increased by a topical alpha-adrenergic agonist, xylometazoline (five control subjects, seven with seasonal rhinitis, studied when asymptomatic) or decreased by topical histamine (eight control subjects). In further experiments, we altered intrapulmonary airway calibre by having subjects inhale histamine or salbutamol aerosols and examined effects on the configuration of nasal flow-volume curves (six subjects with rhinitis and mild asthma). After topical xylometazoline, there was a mean 283% increase in Gnaw, 80% increase in PEFna, and 63% increase in PIFna. After topical histamine, there was a mean 72% decrease in Gnaw, 38% decrease in PEFna, and 39% decrease in PIFna. Inducing intrapulmonary airway obstruction sometimes obscured changes in nasal patency by removing the effects of added nasal resistance on expiration and preventing development of flow limitation in the nose on inspiration. Thus, after topical drug treatment to the nose, changes in Gnaw were considerably larger than in PEFna or PIFna, which were proportionately similar. Because PIFna is usually restricted by nasal flow limitation, it is probably superior to PEFna for assessing nasal patency. When effort is submaximal, intrapulmonary dynamic resistance is increased, or nasal dynamic resistance is low, PEFna and PIFna can give a misleading impression of nasal patency. These errors can be avoided by comparisons with mouth PEF and/or PIF, suggesting that nasal and mouth peak flow should both be measured during home monitoring.

Adult↗

Comparison of four methods of assessing airflow resistance before and after induced airway narrowing in normal subjects.

Four methods for assessing airflow resistance were compared in seven normal adults at baseline and after inducing airway narrowing with inhaled methacholine. Airway resistance (Raw) was measured during panting at 1-2 Hz within a body plethysmograph; total lung resistance was measured by using an esophageal balloon during quiet breathing (RLq) and with doubling of frequency while maintaining the original tidal volume; total respiratory resistance (Rrs) was measured at 6 Hz during forced oscillation applied at the airway opening, and interruption resistance (Rint) was measured at midtidal expiratory flow. Three methods of obtaining Rint after airflow interruption were compared [smooth curve fit of mouth pressure (Pm) back extrapolated to valve closure; two-point linear fit of Pm back extrapolated to 15 ms after closure; and Pm at 100 ms after valve closure]. We found similar basal median values (cmH2O.l-1.s) of Raw (1.3), RLq (1.4), RL of double resting frequency (1.9), Rrs (1.7), and smooth curve fit of Pm back extrapolated to valve closure (1.5); basal values of two-point linear fit of Pm back extrapolated to 15 ms after closure (2.4) and Pm at 100 ms after valve closure (4.4) were considerably larger. After induced airway narrowing, all methods of measuring resistance showed significant increases; these were largest with RLq (median %change of 265) and smallest with the three Rint methods (median %change of 62-72). Rint and Rrs methods had poorer sensitivity for detecting bronchoconstriction than lung resistance of Raw. Of the Rint methods, end interruption pressure was the most sensitive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of posture on respiratory mechanics in obesity.

Increased abdominal mass in obesity should enhance normal gravitational effects on supine respiratory mechanics. We have examined respiratory impedance (forced oscillation over 4-26 Hz applied at the mouth during tidal breathing), maximum inspiratory and expiratory mouth pressures (MIP and MEP), and maximum effort flow-volume curves seated and supine in seven obese subjects (O) (mean age 51 yr, body mass index 43.6 kg/m2) and seven control subjects (C) (mean age 50 yr, body mass index 21.8 kg/m2). Seated mean total lung capacity was smaller in O than in C (82 vs. 100% of predicted); ratio of functional residual capacity (FRC) to total lung capacity averaged 43% in O and 61% in C (P < 0.01). Total respiratory resistance (Rrs) at 6 Hz seated was higher in O (4.6 cmH2O.l-1.s) than in C (2.2 cmH2O.l-1.s; P < 0.001); total respiratory reactance (Xrs) at 6 Hz was lower in O than in C. In C, on changing to the supine posture, mean Rrs at 6 Hz rose to 2.9 cmH2O.l-1.s, FRC fell by 0.68 liter, and Xrs at 6 Hz showed a small fall. In O, despite no further fall in FRC, supine Rrs at 6 Hz increased to 7.3 cmH2O.l-1.s, and marked frequency dependency of Rrs and falls in Xrs developed. Seated, MIP and MEP in C and O were similar; supine there were small falls in MEP and maximum expiratory flow in O. The site and mechanism of the increase in supine Rrs and reduction in supine Xrs and the mechanism maintaining supine FRC in obesity all need further investigation.

Airway Resistance↗

Accuracy and sensitivity of the interrupter technique for measuring the response to bronchial challenge in normal subjects.

The interrupter technique is a non-invasive method for measuring airway calibre. Since the calculation of interrupter resistance (Rint) is critically dependent upon the analysis of the mouth pressure/time (Pmo(t)) curve obtained after flow interruption, we wanted to assess the relative merits of four different analyses of Pmo(t) curves, obtained under basal conditions and following methacholine-induced airway narrowing, in 10 healthy adults. Four methods of analysing the Pmo(t) curves were used to calculate Rint values: RintC-a smooth curve fit with back-extrapolation; RintL-two-point linear fit with back-extrapolation; RintEO-calculated from the pressure change after the post-interruption oscillations had decayed (end-oscillation); and RintEI-calculated from the pressure change at the end of the period of interruption. The airway response measured with the four Rint methods was compared with plethysmographic airway resistance (Raw). The sensitivity of the methods was determined by calculating a sensitivity index (SI), the change in resistance after challenge expressed in multiples of baseline standard deviation. Values of RintC were similar to Raw values under all conditions. Resistance values from the remaining Rint methods significantly exceeded Raw (mean basal difference: 0.13-0.34 kPa.l-1 x s; mean difference after challenge: 0.12-0.42 kPa.l-1 x s. Raw was the most sensitive method for detecting bronchoconstriction (doubling of Raw was equivalent to SI of 10.5). Of the Rint methods, RintEI gave the highest sensitivity index (SI = 3.1), with a 42% mean change; RintC produced the greatest proportionate change after challenge (55%), but with a lower SI (2.2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Paratesticular fibrous pseudotumor in a patient with Gorlin's syndrome: nevoid basal cell carcinoma syndrome.

An 18-year-old man with Gorlin's syndrome (the nevoid basal cell carcinoma syndrome) underwent excisional biopsy of a fibrous pseudotumor of the tunica vaginalis. Preoperative ultrasound confirmed the extraparenchymal nature of this paratesticular lesion, permitting a transscrotal approach. The pathophysiological considerations suggest that this finding (to our knowledge the first such case reported in association with Gorlin's syndrome) may be more than coincidental.

Adult↗

Interaction of unfused tricyclic aromatic cations with DNA: a new class of intercalators.

Unfused tricyclic aromatic ring systems 1-6 with one or two cationic side chains have been synthesized and their interactions with DNA and synthetic polymers probed with a variety of techniques. Molecular mechanics calculations indicate that the torsional angle between ring planes in the minimum energy conformation of the tricyclic molecules can range from 0 degree to as high as 50 degrees depending on the type of rings and substituents. Viscometric titrations with linear and supercoiled DNA, linear dichroism, and NMR studies indicated that all compounds with torsional angles of approximately 20 degrees or less bind to DNA by intercalation. The more highly twisted intercalators caused significant perturbation of DNA structure. Unfused intercalators with twist angles of approximately 20 degrees have reduced binding constants, suggesting that they could not form an optimum interaction with the DNA base pairs. Unfused intercalators with twist less than 20 degrees formed strong complexes with DNA. The structures of these unfused intercalators are more analogous to typical groove-binding molecules, and an analysis of their interaction with DNA provides a better understanding of the subtle differences between intercalation and groove-binding modes for aromatic cations. The results indicate that intercalation and groove-binding modes should be viewed as two potential wells on a continuous energy surface. The results also suggest design strategies for intercalators that can optimally complement DNA base pair propeller twist or that can induce bends in DNA at the intercalation site.

Cations↗

Molecular basis for bleomycin amplification: conformational and stereoelectronic effects in unfused amplifiers.

Sixteen unfused heterobiaromatic and biphenyl compounds substituted with an amino side chain (protonated in water) have been tested for (i) binding with DNA and (ii) their effect on the digestion of the DNA double helix by a bleomycin-iron complex. Only the DNA intercalating molecules amplify the digestion of DNA. One 2,2'-bipyridine derivative tested is an inhibitor of the bleomycin reaction because it removes ferrous ion from the bleomycin complex. Polarity of the intercalating unfused biaromatic system is of primary importance for effective binding of the molecule with native DNA and, at the same time, for its amplification activity. The molecules that have the biaromatic system polarized extensively in the direction of the side cationic chain, so that the intercalating sites constitutes a positive part of the dipole, show strong binding with DNA and good amplification activity. For strong intercalative forces that determine the amplification activity, it is important that both the heteroaromatic subsystems of the molecule have positive ends of their dipoles positioned away from the side chain. This work provides general guidelines for synthesis of new highly effective bleomycin amplifiers.

Bleomycin↗

Selective catalysis of A.T base pair proton exchange in DNA complexes: imino proton NMR analysis.

Polyaromatic molecules with amino chain substituents, upon binding with DNA, selectively catalyze exchange of the A.T base pair protons with bulk water protons. The amine-catalyzed exchange is mediated by compounds which are A.T and G.C base sequence specific, intercalators, and outside binders. A mechanism for the selective exchange, involving transient opening and closing of individual A.T base pairs in the duplex, is discussed.

Adenine↗

Amplification of bleomycin-mediated degradation of DNA.

Three simple and independent tests have been introduced for studying the effect of DNA intercalating compounds on the bleomycin-mediated digestion of DNA in vitro. These methods are based on hyperchromic changes of DNA solution, changes in viscosity of DNA solution, and HPLC quantitative analysis of the four bases released from digested DNA. All three tests give comparable results. However, the viscometric method is technically the simplest and at the same time the most sensitive. The amplification of the bleomycin-mediated degradation of DNA by three unfused heteropolyaromatic intercalator molecules, namely N-[2''-(dimethylamino)ethyl]-4-thien-2'-ylpyrimidin-2-amine (1N), N,N-dimethyl-2-[(4'-thien-2''-ylpyrimidin-2'-yl)thio] ethylamine (1S), and newly synthesized 2,5-bis[2'-[[2''-(dimethylamino)ethyl]thio]pyrimidin-4'yl]thiophene (2) correlates well with the respective DNA binding constants for these compounds and is concentration dependent. The amplification activity of these compounds increases with increasing concentrations. The strongly binding compound 2 is the best amplifier of bleomycin in vitro found so far. Fused heteropolyaromatic systems, like ethidium bromide, are modest amplifiers of bleomycin at low concentrations but strongly inhibit the bleomycin chemistry at high concentrations.

Animals↗

Home hyperalimentation for common variable hypogammaglobulinemia with malabsorption secondary to intestinal nodular lymphoid hyperplasia.

Common variable hypogammaglobulinemia (immunodeficiency), a disorder characterized by late-onset immunoglobulin deficiency and lack of humoral immunity, has a variable association with bronchiectasis, cholelithiasis, nodular lymphoid hyperplasia, gastrointestinal neoplasia, megaloblastic anemia, and malabsorption. The patient described in this report had all of the above except neoplasia. In addition, he had calcium oxalate renal stones probably secondary to his malabsorption. The first case demonstrating the beneficial effect of home hyperalimentation in patients with severe malabsorption refractory to other treatments is described. Home hyperalimentation overnight allows the patient freedom for daily activities while also being more cost-effective than in-hospital parenteral nutrition.

Activities of Daily Living↗