Biomedical subjects

W R Wilson

Publications and source records attributed to W R Wilson.

At least 163 records · Page 9Linked to original sources

PubMed1991

Resternotomy in patients with valved conduits adherent to the sternum.

Twenty-two patients with valved conduits adherent to the sternum underwent resternotomy. Mean age was 10 +/- 6 years, and mean conduit age was 4 +/- 4 years. Diagnoses were D-transposition (7), truncus arteriosus (7), univentricular heart (6), Taussig-Bing anomaly (1), and corrected transposition (1). The majority of patients (68%) had reoperation for outgrown or degenerated conduits. In 17 patients, the sternum was opened with a chisel. Two of these patients sustained conduit neointimal collapse from manipulation, and 3 had conduit tear requiring immediate cardiopulmonary bypass through the femoral vessels. In the last 5 patients, the sternum was opened above and below the conduit, and the inner table was chiseled and left attached to the conduit avoiding injury and undue conduit manipulation. Cardiopulmonary bypass and operation were carried out uneventfully. We believe that the recent technique described provides a safe alternative approach to valved conduits adherent to the sternum.

Adolescent↗

PubMed1991

Extended aortic valvuloplasty: a new approach for the management of congenital valvar aortic stenosis.

A new technique for the treatment of congenital valvar aortic stenosis is described. It consists of augmenting the aortic cusp by extending the commissurotomy incision into the aortic wall around the leaflet insertion, mobilizing the valve cusp attachment at the commissures, and freeing the aortic insertion of the rudimentary commissure. The results of standard valvotomy performed on 48 patients (group 1) were compared with those of the new extended valvuloplasty carried out on 16 patients (group 2). The two groups were comparable in age at operation (2.7 +/- 2.1 years for group 1 versus 2.1 +/- 1.7 years for group 2; p = not significant) and in preoperative pressure gradient (58 +/- 25 mm Hg for group 1 versus 61 +/- 36 mm Hg for group 2; p = not significant). There was no operative mortality in either group. Follow-up is available on all patients, with a mean of 4.3 +/- 2.6 years for group 1 versus 1.7 +/- 0.5 years for group 2 (p = 0.05). There was one late death in group 1. Postoperative gradient was 47 +/- 13 mm Hg in group 1 versus 19 +/- 13 mm Hg in group 2 (p = 0.05). Moderate or severe regurgitation was present in 18 patients (38%) in group 1 and 2 patients (13%) in group 2 (p = not significant). Reoperation was needed in 8 patients (17%) in group 1 versus 2 patients (13%) in group 2 (p = not significant). The described valvuloplasty procedure addresses the unique pathological features of valvar aortic stenosis and provides better relief of the obstruction than the presently available techniques. Longer follow-up is needed to determine the late results of this approach.

Aortic Valve↗

PubMed1991

The Damus-Stansel-Kaye procedure: anatomical determinants and modifications.

Seven of 119 patients undergoing anatomical correction for transposition of the great arteries and Taussig-Bing anomalies without pulmonary stenosis had the Damus-Stansel-Kaye procedure and the rest, the arterial switch. The age of the patients having the Damus-Stansel-Kaye procedure ranged from 0.5 year to 5 years (mean age, 2.2 +/- 1 years). Four patients had transposition, 2 had Taussig-Bing anomaly, and 1 had corrected transposition. Indications for the Damus-Stansel-Kaye procedure were side-by-side great arteries associated with difficult coronary anatomy (5 patients), single coronary system (1 patient), and subaortic stenosis (1). A graft between the ascending and descending aorta for interrupted aortic arch made mobilization and posterior displacement of the ascending aorta for the arterial switch difficult. Subaortic stenosis (1 patient), subpulmonary ventricular septal defect (2 patients), and restrictive ventricular septal defect (4) precluded the Rastelli procedure. In 6 patients, the main pulmonary artery was transected at the band, a proximal main pulmonary artery to aorta anastomosis was complemented with a synthetic patch, and a right ventricle to distal main pulmonary artery valved conduit was inserted. Four patients had closure of the aortic outflow. Two patients had postoperative bleeding and 2, heart block. The only patient who did not have transection of the main pulmonary artery, an omission that led to an obstructed conduit at the distal anastomosis, died late. Two patients subsequently needed aortic outflow closure for critical aortic insufficiency. The Damus-Stansel-Kaye procedure has a definite role and can be safely performed in patients with transposition of the great arteries and Taussig-Bing anomalies.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

PubMed1991

Advantages of early relief of subaortic stenosis in single ventricle equivalents.

Thirteen patients with single ventricle equivalents and subaortic stenosis underwent relief of the stenosis and subsequent Fontan operation. Nine patients, group 1, had the obstruction relieved at 3.6 +/- 1.6 years of age whenever the pressure gradient became apparent. Four patients, group 2, had the subaortic stenosis operated on at the neonatal period, 10.5 +/- 10 days old, before hemodynamic evidence of obstruction. Preoperative pressure gradient across the outflow tract was 44.2 +/- 4.7 mm Hg in group 1 versus 4.7 +/- 5 mm Hg in group 2 (p = 0.002). Ventricular muscle mass was 186% +/- 18% in group 1 versus 114% +/- 5% of normal in group 2 (p = 0.0001), and mass/volume ratio was 1.12 +/- 0.62 in group 1 versus 0.62 +/- 0.16 in group 2 (p = 0.003). Relief of subaortic stenosis was achieved by proximal pulmonary artery to ascending aorta or aortic arch anastomosis and by systemic to distal pulmonary artery shunt. There was no hospital mortality or complication related to the procedure. At evaluation before Fontan operation, 4.3 +/- 1.6 years after relief of subaortic stenosis in group 1 and 3.2 +/- 0.9 years in group 2, the pressure gradient across the ventricular outflow tract was 4 +/- 3 mm Hg in group 1 versus 3 +/- 2 mm Hg in group 2 (p = not significant), ventricular muscle mass was 184% +/- 31% in group 1 versus 114% +/- 5% of normal in group 2 (p = 0.003), and the mass/volume ratio was 1.17 +/- 0.2 in group 1 versus 0.62 +/- 0.2 in group 2 (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗

PubMed1991

Surgical options in subaortic stenosis associated with endocardial cushion defects.

Over a 15-year period, 12 patients with endocardial cushion defects undergoing correction had subaortic stenosis requiring operative intervention. Ages ranged from 4 months to 17 years (mean, 7 +/- 6 years) and subaortic gradients from 15 to 100 mm Hg (mean, 60 +/- 25 mm Hg). Subaortic stenosis was due to discrete fibromuscular tissues in 7 patients, mitral valve malattachment in 3, and tunnel outflow in 2. In 2, the subaortic stenosis was clinically significant at the time of endocardial cushion defects repair, whereas in 10 it was noted 2 to 14 years postoperatively (mean, 6.3 +/- 5 years). Surgical relief of subaortic stenosis was accomplished by resection of muscle tissues in 7, apicoaortic conduit insertion in 2, modified Konno procedure (aortic valve preserved) in 2, and lifting of malattached mitral valve from the outflow in 1. There was no early death and one late death (infected conduit). Severe mitral insufficiency developed in the patient who had the mitral valve lifted and necessitated valve replacement. Postoperative echocardiographic gradient in 9 patients ranged from 0 to 36 mm Hg (mean, 10.5 +/- 14 mm Hg). Clinically significant subaortic stenosis has not developed in any patient in 15 years of follow-up (mean, 5 +/- 4 years). We conclude that in subaortic stenosis associated with endocardial cushion defects, resection is effective for discrete obstruction, whereas a modified Konno procedure is preferable for obstruction due to tunnel outflow or mitral valve malattachment.

Aortic Valve Stenosis↗

PubMed1991

Tetracyclines, chloramphenicol, erythromycin, clindamycin, and metronidazole.

The tetracyclines are effective in the treatment of Chlamydia, Mycoplasma pneumoniae, and rickettsial infections and also can be used for gonococcal infections in patients unable to tolerate penicillin. These drugs may cause gastrointestinal irritation, diarrhea, phototoxic dermatitis, and vestibular damage, and fatal reactions due to hepatotoxicity have occurred in pregnant women. Chloramphenicol has a broad spectrum of bacteriostatic activity, but its association with suppression of the bone marrow and aplastic anemia has relegated it to a historical role. Erythromycin is the drug of choice for the treatment of infections caused by M. pneumoniae, Legionella species, group A beta-hemolytic streptococci, and Streptococcus pneumoniae. The frequency of serious adverse effects associated with the use of erythromycin is low; dose-related epigastric distress may occur. Clindamycin is bactericidal to most nonenterococcal gram-positive aerobic bacteria and many anaerobic microorganisms. Although historically it was a frequent cause of antibiotic-associated diarrhea and colitis, clindamycin is considered an excellent alternative to beta-lactam antibiotics for treatment of many staphylococcal infections, and it has therapeutic utility in anaerobic infections and in several protozoan infections in immunosuppressed patients. Metronidazole is efficacious for treating nonpulmonary anaerobic infections, various parasitic infections (trichomoniasis, amebiasis, and giardiasis), nonspecific vaginitis, and Clostridium difficile-mediated colitis. With use of metronidazole, mild side effects such as epigastric discomfort, diarrhea, reversible neutropenia, and allergic-type cutaneous reactions may occur.

Chloramphenicol↗

PubMed1991

DNA-directed alkylating agents. 4. 4-anilinoquinoline-based minor groove directed aniline mustards.

A series of 4-anilinoquinoline-linked aniline mustards of widely varying mustard reactivity were prepared and evaluated for their antitumor activity. The compounds were designed as minor grove binding agents, where the aniline mustard ring is itself part of the DNA-binding ligand. While there was a general trend for cytotoxicity to correlate with mustard reactivity, this was much less pronounced than with untargeted mustards. The compounds were much more cytotoxic than the parent diols, and were also at least 10-fold more cytotoxic than the corresponding aniline mustards themselves. Comparative cell line studies suggested that the mechanism of cytotoxicity varied with mustard reactivity. The most reactive mustards cross-linked DNA, while cell killing by the less reactive compounds appeared to be by the formation of bulky monoadducts. The compounds were active but not particularly dose-potent against P388 leukemia in vivo. The modest potency may be related to their poor aqueous solubility, since the more soluble methyl quaternary salts were equally active at much lower doses.

Alkylating Agents↗

PubMed1991

Serodiagnosis of Helicobacter pylori: comparison of enzyme-linked immunosorbent assays.

Enzyme-linked immunosorbent assays (ELISAs) have been developed to diagnose Helicobacter pylori infection. However, the methods are not standardized. We therefore prospectively evaluated the sensitivities and specificities of ELISAs developed in the United States and the United Kingdom in a study population comprising 41 consecutive symptomatic outpatients and 35 volunteers. At endoscopy, multiple biopsies were obtained for histology and culture and stained sections were graded for chronic gastritis, active chronic gastritis, and density of H. pylori. Serum samples were analyzed for H. pylori by ELISA. The first set of assays for immunoglobulin G (IgG) and IgA used a pool of sonicated isolates of H. pylori from five patients in the United States (antigen A). The second set of assays, developed in the United Kingdom, used three different antigens: antigen 1, an acid-extractable surface antigen; antigen 2, an acid-extractable antigen from an aflagellate variant; and antigen 3, a urease-containing fraction. Cutoff scores for positive results were determined a priori on the basis of previous serological studies. There was close agreement between histology and culture. In the study population, 36% of the individuals were H. pylori positive. The diagnostic value of the different ELISAs were highly comparable, and the crude antigens performed as well as the more purified antigens. The antigen A IgG had a sensitivity and specificity of 96 and 94%, respectively; the values for antigen 1 were 93 and 96%, respectively. The antigen A IgA and antigen 3 assays were the least sensitive tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Prospective evaluation of the risk of bacteremia associated with transesophageal echocardiography.

BACKGROUND: Transient bacteremia may lead to endocarditis in patients with significant valvular lesions. METHODS AND RESULTS: Because transesophageal echocardiography selects a patient population with a high prevalence of valvular lesions, we prospectively evaluated the risk of transient bacteremia associated with transesophageal echocardiography in 49 patients. Blood cultures were obtained immediately before transesophageal echocardiography and at 5, 10, and 20 minutes after the start of the procedure. For each culture, 30 ml venous blood was obtained and 10 ml was inoculated into each of an Isolator tube, Septi-chek bottle, and a nonvented Trypticase soy broth bottle. Broth cultures were incubated for 14 days. Blood from the Isolator tube was plated onto appropriate media for recovery of bacteria and fungi. Two patients were excluded from analysis because the final two sets of blood cultures could not be obtained. Among the remaining 47 study patients, two preprocedure control blood cultures were positive, and two of 141 subsequent cultures were positive. All isolates were considered contaminants. Thus, we found no significant bacteremia due to pathogenic oral flora during transesophageal echocardiography (0%; 95% CI, 0.0-7.5%). CONCLUSIONS: Although recommendations for antimicrobial prophylaxis for transesophageal echocardiography should be individualized for each patient, many patients may not require antimicrobial prophylaxis.

Adult↗

PubMed1991

Behavioral audiometry.

Behavioral audiometry is based on observation of overt responses to controlled auditory stimuli, as contrasted with electrophysiologic procedures, which involve electrophysiologic monitoring or direct recording of the bioelectric correlates of the original signal. When reinforcement is added to the behavioral procedures, the infant or young child provides highly reliable responses, and it is possible to test most infants 6 months of age and older with these procedures. The combination of both behavioral and electrophysiologic procedures can resolve most clinical questions regarding the auditory function of young infants and children.

Acoustic Stimulation↗

PubMed1991

Conal enlargement for diffuse subaortic stenosis.

Twelve patients underwent conal enlargement for diffuse subaortic stenosis over a 3 1/2-year period. The subaortic stenosis was due to tunnel outflow in 11 and malattached mitral valve in one. Mean age was 4.4 +/- 4 years and mean subaortic gradient was 50 +/- 21 mm Hg. Three infants had a malalignment ventricular septal defect. In eight patients significant obstruction occurred 2 to 7 years (mean 4 +/- 2) after simple resection of subaortic stenosis (n = 2), ventricular septal defect closure (n = 2), ventricular septal defect closure and subaortic stenosis resection (n = 2), and canal repair (n = 2). In three infants the tunnel outflow distal to a malalignment ventricular septal defect was enlarged and closed with the defect. In three patients with subaortic stenosis proximal to a previously repaired ventricular septal defect, transatrial conal enlargement through the ventricular septal defect was performed. Another patient without a ventricular septal defect had transatrial conal enlargement. The remaining five patients had the modified Konno procedure. Two patients had postoperative complete heart block and one infant had insertion of an apicoaortic conduit for aortic anulus hypoplasia 9 months later. One patient died of pneumonia during the follow-up period. Postoperative echographic outflow gradients up to 3 1/2 years (mean 1.2 +/- 1) ranged up to 25 mm Hg (mean 7 +/- 11) and were mainly at the aortic level. The 11 surviving patients are doing well up to 3 1/2 years of follow-up (mean 1.5 +/- 1). We conclude that conal enlargement procedures with aortic valve preservation are preferable, effective, and can be safely performed for diffuse subaortic stenosis in infants and children.

Aortic Valve↗

PubMed1991

Treatment of infections caused by anaerobes.

In summary, the selection of a specific antimicrobial agent for the treatment of infections caused by anaerobic microorganisms depends upon the site of infection, the suspected anaerobic and aerobic microorganisms causing the infection, and the pharmacokinetics and drug distribution of the antimicrobial agent. Appropriate surgical debridement or drainage of abscess material is as important, if not more so, than the selection of a specific antimicrobial agent for the successful management of patients with infections caused by anaerobic microorganisms. The availability of new antimicrobials with activity against anaerobic microorganisms, and combination therapy for managing infection caused by mixed flora of aerobic and anaerobic microorganisms, has increased our ability to successfully manage hospitalized patients with infections caused by these microorganisms.

Abdomen↗

PubMed1990

Ocular involvement in patients with onchocerciasis after repeated treatment with ivermectin.

We assessed ocular changes after therapy at six and 12 months with ivermectin (150 micrograms/kg of body weight) in a 12-month prospective study of 29 patients with ocular onchocerciasis and 15 patients with onchocerciasis without ocular involvement. The patients lived in a hyperendemic area in Sierra Leone, West Africa, where no vector control was instituted. Five months after initial treatment, the microfilarial load in skin and eyes had decreased significantly (P less than .0000), but 28 of 44 (63%) patients had positive skin-snip test results and nine of 29 (31%) patients with ocular involvement had active ocular disease. Twelve months after initial treatment, 15 of 41 (37%) patients had positive skin-snip test results and eight of 26 (31%) showed active ocular involvement. All patients with persistent ocular disease after therapy showed evidence of active onchocerciasis at that time, which suggests that a dose of ivermectin at six-month intervals is not sufficient for intensely infested patients with severe ocular disease. We developed an ocular involvement score to evaluate the patient's total ocular status and observed a significant relation between the pretreatment severity of ocular involvement and the persistence of active ocular disease after treatment with ivermectin.

Adolescent↗

PubMed1990

The fate of N1'-methanesulphonyl-N4'-(9-acridinyl)-3'-methoxy-2',5'-cyclohexadiene- 1',4'-diimine (m-AQDI), the primary oxidative metabolite of amsacrine, in transformed Chinese hamster fibroblasts.

The cytotoxicity of the anti-leukaemia drug amsacrine (m-AMSA) has been suggested to result from its oxidative metabolism to the corresponding quinonediimine, N1'-methanesulphonyl-N4'-(9-acridinyl)-3'-methoxy-2',5'-cyclohexad iene-1',4'- diimine (mAQDI). The metabolic fate of mAQDI was examined in cultured CHO cells (subline AA8) to identify the end products to be expected following oxidative metabolism of m-AMSA. [Acridinyl-G-3H]-m-AQDI was rapidly accumulated by AA8 cells in phosphate buffered saline with complete conversion in less than one minute to m-AMSA, macromolecular adducts and polar low molecular weight species, each of these three classes being formed in approximately equal amounts. Two of the polar products were chromatographically identical to those formed on reaction of m-AQDI with reduced glutathione. These were identified by 1H NMR spectroscopy as the 1,4-addition product 5'-(S-glutathionyl)-m-AMSA and the previously unreported isomeric 6'-(S-glutathionyl)-m-AMSA. These thiol adducts were also formed rapidly from m-AQDI in deproteinized cell lysates indicating a non-enzymatic process, although the possibility of enzymatic catalysis in intact cells has not been eliminated. The absence of such products in AA8 cells after treatment with m-AMSA places an upper limit of 1% per hour on the rate of its oxidative metabolism in these cells and suggests that generation of m-AQDI is unlikely to be responsible for the cytotoxicity of m-AMSA in cultured tumour cells.

Amsacrine↗

PubMed1990

Decrease in adverse reactions after repeated ivermectin treatment in onchocerciasis.

We assessed the side-effects after multiple single-dose treatment with ivermectin (150 micrograms/kg) in onchocerciasis patients form a hyperendemic area in Sierra Leone, in order to investigate whether medical surveillance was always necessary. After initial treatment 87 onchocerciasis patients were examined for adverse reactions. Fourty-four of these 87 patients (51%) received a second dose of ivermectin 5 months later and thirty-five (40%) received a third dose one year later. The side-effects after the second and third doses were significantly diminished, when compared with the initial dose of ivermectin in the treatment of onchocerciasis (chi2 test p less than 0.005, resp. p less than 0.008). Side-effects requiring therapy were observed in 32% of patients after the first dose, in 18% after the second dose and in 11% after the third dose of ivermectin. Severe side-effects (9%) were only seen after the initial ivermectin dose. All the severe adverse reactions appeared within 48 hours. In view of our findings, it seems necessary that the first treatment with ivermectin should take place under strict medical supervision during at least two days. Five months after treatment with a single dose of ivermectin 29 out of 44 patients (66%) still had a positive skin-snip test. Seven months after the second dose 15 of 35 patients (43%) had a positive skin-snip count. Since almost half of the patients had a positive skin-snip test despite two treatments with ivermectin, it could be argued that in hyperendemic areas treatment should consist of at least two doses in the first year.

Administration, Oral↗

PubMed1990

[14C]urea breath test for diagnosis of Helicobacter pylori.

H. pylori is a potent urease producer, a characteristic that has been exploited in the development of the [14C]- and [13C]urea breath tests. The prevalence of H. pylori infection also is known to increase with advancing age; however, the individual patient's age has not routinely been considered when interpreting urea breath test results. The aim of this study was to validate a short, age-adjusted [14C]urea breath test for use in diagnosing H. pylori infections. Forty-one subjects (28 volunteers, 13 patients) underwent esophagogastroduodenoscopy with biopsies. Subjects were defined as being H. pylori-positive if histology or culture was positive. In addition, all subjects completed a 120-min [14C]urea breath test. A logistic regression analysis adjusting for age was used to estimate the probability of H. pylori positivity as a function of the 14C values generated. Sixteen subjects were H. pylori-positive, and 25 were H. pylori-negative. The 14C values generated between 15 and 80 min were found to be equally predictive in identifying H. pylori-positive subjects. Advancing age was associated with a higher probability of H. pylori-positivity. By taking advantage of the statistical probabilities, older patients could be accurately diagnosed with H. pylori at lower 14C values. We found that [14C]urea breath test to be both a sensitive and specific test that can be abbreviated to a 30-min examination (total test time). Moreover, our mathematical model indicates that a patient's age should be considered in order to optimize interpretation of the [14C]urea breath test, although further observations are needed to confirm this model.

Age Factors↗

PubMed1990

Influence of referral bias on the apparent clinical spectrum of infective endocarditis.

PURPOSE: To assess the effect of referral bias on the clinical spectrum of infective endocarditis. PATIENTS AND METHODS: We performed a retrospective study comparing a population-based cohort of incidence cases from Olmsted County, Minnesota, with a cohort of referred cases from the practice of the Mayo Clinic during the period from 1970 to 1987. RESULTS: In the community cohort, age was an important risk factor for acquiring endocarditis (incidence rate ratio 8.8:1 for age 65 years or older versus age less than 65 years), but episodes in elderly patients were underrepresented in the referral practice. The proportion of cases due to Staphylococcus aureus was greater in the community than in the referral practice (p less than 0.02), while a trend toward overrepresentation of enterococcal endocarditis was seen in the referral population (p = 0.057). Symptom duration prior to diagnosis was significantly shorter in the community. Overall, measures of in-hospital morbidity and mortality were similar in the two populations, but advanced age was associated with adverse outcome in the community cohort. CONCLUSION: The clinical spectrum of infective endocarditis may be distorted by referral. The increased risk of endocarditis in the elderly underscores the importance of adherence to recommendations for prophylaxis in this patient population.

Adolescent↗

PubMed1990

Hypoxia-selective antitumor agents. 3. Relationships between structure and cytotoxicity against cultured tumor cells for substituted N,N-bis(2-chloroethyl)anilines.

A series of aniline mustards with a wide range of electron-donating and -withdrawing substituents in the 3- and 4-positions has been synthesized and evaluated for cytotoxicity in cell culture to examine the potential of using nitro group deactivated nitrogen mustards for the design of novel hypoxia-selective anticancer drugs (Denny, W. A.; Wilson, W. R. J. Med. Chem. 1986, 29, 879). Hydrolytic half-lives in tissue culture media, determined by bioassay against a cell line (UV4) defective in the repair of DNA interstrand cross-links showed the expected dependence on the Hammett electronic parameter, sigma, varying from 0.13 h for the 4-amino analogue to greater than 100 h for analogues with strongly electron-withdrawing substituents. Cytotoxic potencies in aerobic UV4 cultures showed a similar dependence on sigma. This dependence predicted that the 4-nitroaniline mustard would be 7200-fold less potent than its potential six-electron reduction product, the 4-amino compound, in growth inhibition assays using a 1-h drug exposure. The measured differential was much lower (225-fold) because of the instability of the latter compound, but a differential of 17,500-fold was observed in the initial rate of killing by using a clonogenic assay. The potential for formation of reactive mustards by reduction to the amine or hydroxylamine was demonstrated by the 4-nitroso compound, which had an aerobic toxicity similar to that of the amine. Although these features confirmed the original rationale, the 3-nitro- and 4-nitroaniline mustards had only minimal hypoxic selectivity against UV cells. Toxicity to hypoxic cells appears to be limited by the low reduction potentials of these compounds and consequent lack of enzymatic nitroreduction. However, this study has demonstrated that nitro groups can be used to latentiate aromatic nitrogen mustards and indicates that examples with higher reduction potentials could provide useful hypoxia-selective therapeutic agents.

Alkylation↗