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Biomedical subjects

M C Harrison

Publications and source records attributed to M C Harrison.

11 recordsLinked to original sources

The prevalence of women with breast implants in the United States--1989.

Most estimates of the number of women with breast implants appear to be extrapolations of industry or clinical data. While both provide valuable information, the former about the total number of devices ever produced or sold and the latter about the cumulative number of surgeries performed, neither can be used to directly estimate the prevalence of women with silicone gel or saline implants. In 1989, Market Facts, Inc., conducted a mail survey of 40,000 households chosen as representative of the population of the United States and received responses from 70.7%. Overall, the prevalence was 8.08 per 1,000 women with about 60% of the devices reportedly implanted for cosmetic reasons. The procedure was more common among Whites of the higher socio-economic classes. Based upon the results of this survey, the total number of US women in 1989 with breast implants was estimated to be 815,700 (95% confidence interval: 715,757-924,729).

Adolescent↗

The breast implant controversy.

The breast implant issue is a "bad news/good news" story. For many women with implants, the controversy has caused a fair degree of anxiety which may or may not be resolved as further information becomes available. It has also taken its toll on Dow Corning. Whole lines of medical products have been eliminated or are being phase out. The development of new medical applications has been terminated. As a consequence, employees have lost their jobs. What the effect will be on the biomedical industry as a whole remains to be seen (11). While silicones have been an important component in various medical devices, it is likely that other materials can be used as replacements. However, suppliers of non-silicone materials are also reevaluating their role in this market. For example, Du Pont, the nation's largest chemical company, has determined that the unpredictable and excessive costs of doing business with manufacturers of implantable medical devices no longer justifies the unrestricted sale of standard raw materials into this industry. Other companies are quietly following suit. On the up side, it is possible that the research being driven by this controversy will result in a greater understanding of the immunologic implications of xenobiotics, of the importance of nonbiased observations, of the need for ready access to valid data sets, and of the opportunity for valid scientific information to guide legal decisions. Only time will tell.

Animals↗

Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: results of the PROVED trial. PROVED Investigative Group.

OBJECTIVES: The purpose of this study was to determine whether digoxin is effective in patients with chronic, stable mild to moderate heart failure. BACKGROUND: Digoxin has been a traditional therapy in heart failure, but methodologic limitations in earlier studies have prevented definitive conclusions regarding its efficacy. METHODS: Withdrawal of digoxin (placebo group, n = 46) or its continuation (digoxin group, n = 42) was performed in a prospective, randomized, double-blind, placebo-controlled multicenter trial of patients with chronic, stable mild to moderate heart failure secondary to left ventricular systolic dysfunction who had normal sinus rhythm and were receiving long-term treatment with diuretic drugs and digoxin. RESULTS: Patients withdrawn from digoxin therapy showed worsened maximal exercise capacity (median change in exercise time -96 s) compared with that of patients who continued to receive digoxin (change in exercise time +4.5 s) (p = 0.003). Patients withdrawn from digoxin therapy showed an increased incidence of treatment failures (p = 0.039) (39%, digoxin withdrawal group vs. 19%, digoxin maintenance group) and a decreased time to treatment failure (p = 0.037). In addition, patients who continued to receive digoxin had a lower body weight (p = 0.044) and heart rate (p = 0.003) and a higher left ventricular ejection fraction (p = 0.016). CONCLUSIONS: These data provide strong evidence of the clinical efficacy of digoxin in patients with normal sinus rhythm and mild to moderate chronic heart failure secondary to systolic dysfunction who are treated with diuretics.

Body Weight↗

Novel spirosuccinimides with incorporated isoindolone and benzisothiazole 1,1-dioxide moieties as aldose reductase inhibitors and antihyperglycemic agents.

Compounds from two novel series of spirosuccinimides were prepared. Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group. These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. Many members from the isoindolone series 2, particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency. The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer. Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg). Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone. However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.

Aldehyde Reductase↗

Syntheses of tolrestat analogues containing additional substituents in the ring and their evaluation as aldose reductase inhibitors. Identification of potent, orally active 2-fluoro derivatives.

A series of aldose reductase inhibitors were prepared which were analogues of the potent, orally active inhibitor tolrestat (1). These compounds (5, 7, 9, and 10) have an extra substituent on one of the unoccupied positions on the naphthalene ring of 1. Primary amide prodrugs of several members from the series 5 and 7, namely 6 and 8, respectively, were also prepared. These compounds were evaluated in two in vitro systems: an isolated enzyme preparation from bovine lens to assess their intrinsic inhibitory activity and an isolated sciatic nerve assay to determine their ability to penetrate membranes of nerve tissue. These compounds were also evaluated in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. In general, compounds in series 5, 7, 9, and 10 were potent inhibitors of bovine lens aldose reductase. 2-Halo-substituted analogues from the series 5, 7, and 9 exhibited high activity in the nerve of the 4-day-galactose-fed rat, and in several instances, the primary amide prodrug 8 enhanced the in vivo potency of the respective carboxylic acid 7. Two 2-fluoro-derivatives, 8a and 9a, had especially high activity in vivo and were chosen for additional studies. These compounds were found to be approximately equipotent to tolrestat in the sciatic nerve of the galactose-fed rat and the STZ rat, as judged by their ED50's in these assays. Although primary amide analogue 8a did not have intrinsic inhibitory activity toward aldose reductase, it was metabolized to an active form in vivo and also in vitro within the sciatic nerve.

Administration, Oral↗

Blood lead levels in children in the north-west of Adelaide.

Capillary blood lead levels were investigated in a sample of 513 children of preschool age who were drawn from an industrial working-class region of Adelaide. The geometric mean lead level was 16.3 micrograms/dL. Fourteen children (2.7%) had a blood lead level of at least 30 micrograms/dL, which is designated by the National Health and Medical Research Council as "the level of concern". Boys tended to have higher lead levels than did girls, and children who lived closer to the inner city generally had higher levels than did those who lived further away. Compared with most other Australian findings, the blood lead levels in this study tended to be high. We suspect that the age groups that were studied, and the industrial urban quality of the region that was included, would have had an important bearing on this finding. However, the proportion of children with elevated lead levels in this study did not seem high when compared with US data for children in a comparable age range.

Australia↗