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Biomedical subjects

M DeLuca

Publications and source records attributed to M DeLuca.

At least 19 recordsLinked to original sources

Putative contributors to the secular increase in obesity: exploring the roads less traveled.

OBJECTIVE: To investigate plausible contributors to the obesity epidemic beyond the two most commonly suggested factors, reduced physical activity and food marketing practices. DESIGN: A narrative review of data and published materials that provide evidence of the role of additional putative factors in contributing to the increasing prevalence of obesity. DATA: Information was drawn from ecological and epidemiological studies of humans, animal studies and studies addressing physiological mechanisms, when available. RESULTS: For at least 10 putative additional explanations for the increased prevalence of obesity over the recent decades, we found supportive (although not conclusive) evidence that in many cases is as compelling as the evidence for more commonly discussed putative explanations. CONCLUSION: Undue attention has been devoted to reduced physical activity and food marketing practices as postulated causes for increases in the prevalence of obesity, leading to neglect of other plausible mechanisms and well-intentioned, but potentially ill-founded proposals for reducing obesity rates.

Age Factors↗

Measuring the genetic influence in modulating the human life span: gene-environment interaction and the sex-specific genetic effect.

New approaches are needed to explore the different ways in which genes affect the human life span. One needs to assess the genetic effects themselves, as well as gene-environment interactions and sex dependency. In this paper, we present a new model that combines both genotypic and demographic information in the estimation of the genetic influence on life spans. Based on Cox's proportional hazard assumption, the model measures the risks for each gene as well as for gene-environment and gene-sex interactions, while controlling for confounding factors. A two-step MLE is introduced to obtain a non-parametric form of the baseline hazard function. The model is applied to genotypic data from Italian centenarian studies to estimate relative risks of candidate genes, risks due to interactions and initial frequencies of different genes in the population. Results from models that either do or do not take into consideration individual heterogeneity are compared. It is shown that ignoring the existence of heterogeneity can lead to a systematic underestimation of genetic effects and effects due to interactions.

Alleles↗

Enhancement of bone growth by sustained delivery of recombinant human bone morphogenetic protein-2 in a polymeric matrix.

PURPOSE: The purpose of this study was to develop a polymeric sustained delivery system for recombinant human bone morphogenetic protein-2 (BMP-2) and to evaluate local bone growth induced by the sustained release of BMP-2 in an animal model. METHODS: BMP-2 was incorporated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microspheres to obtain different release rates. Two sustained and an immediate release implants were produced by suspending the BMP-2 loaded PLGA microspheres in aqueous sodium carboxymethylcellulose (CMC), lyophilizing, and cutting the dried materials to the size of the animal bone defects. The local in vivo release at the implantation site in rat calvarial defects was determined by gamma scintigraphy using radiolabeled BMP-2. The local bone induction in the critical size of rabbit calvarial defects was evaluated six weeks post implantation. RESULTS: The immediate release implant showed about 65% initial drug release within 24 h and the remaining BMP-2 quickly exhausted from the implantation site within 7 days. The sustained release implants, showing 45-55% initial release followed by a prolonged release for 21 days, released a greater amount of BMP-2 at the implantation site and maintained higher serum BMP-2 for the longer period of time compared to the immediate release implant. Significant bone growth was observed in all BMP-2 treated defects while the defects without treatment or with BMP-2-free implant showed minimal bone healing. 75-79% of rabbit calvarial defect area was healed with newly induced bone matrix by the sustained release implants in 6 weeks as compared to 45% recovery from the immediate release implant. CONCLUSION: The sustained delivery of BMP-2 based on the biodegradable PLGA microsphere system resulted in faster and more complete bone healing in the animal model.

Animals↗

Hypertrophic cardiomyopathy. Tools for identifying risk and alleviating symptoms.

Hypertrophic cardiomyopathy is characterized by left or right ventricular hypertrophy that is usually asymmetric and involves the interventricular septum. The condition has numerous genetic, anatomic, and clinical variations and continues to stimulate interest and investigation into causes and treatment options. New genetic forms of the disorder are being identified because of the rapid growth of molecular genetics. However, even with technological advances and a large database of information, risk stratification and treatment of hypertrophic cardiomyopathy remain difficult and controversial. Because of the high risk of sudden death, it is imperative that patients be advised against participation in competitive sports.

Cardiomyopathy, Hypertrophic↗

Genes, demography, and life span: the contribution of demographic data in genetic studies on aging and longevity.

In population studies on aging, the data on genetic markers are often collected for individuals from different age groups. The purpose of such studies is to identify, by comparison of the frequencies of selected genotypes, "longevity" or "frailty" genes in the oldest and in younger groups of individuals. To address questions about more-complicated aspects of genetic influence on longevity, additional information must be used. In this article, we show that the use of demographic information, together with data on genetic markers, allows us to calculate hazard rates, relative risks, and survival functions for respective genes or genotypes. New methods of combining genetic and demographic information are discussed. These methods are tested on simulated data and then are applied to the analysis of data on genetic markers for two haplogroups of human mtDNA. The approaches suggested in this article provide a powerful tool for analyzing the influence of candidate genes on longevity and survival. We also show how factors such as changes in the initial frequencies of candidate genes in subsequent cohorts, or secular trends in cohort mortality, may influence the results of an analysis.

Aging↗

Contrast limited adaptive histogram equalization image processing to improve the detection of simulated spiculations in dense mammograms.

The purpose of this project was to determine whether Contrast Limited Adaptive Histogram Equalization (CLAHE) improves detection of simulated spiculations in dense mammograms. Lines simulating the appearance of spiculations, a common marker of malignancy when visualized with masses, were embedded in dense mammograms digitized at 50 micron pixels, 12 bits deep. Film images with no CLAHE applied were compared to film images with nine different combinations of clip levels and region sizes applied. A simulated spiculation was embedded in a background of dense breast tissue, with the orientation of the spiculation varied. The key variables involved in each trial included the orientation of the spiculation, contrast level of the spiculation and the CLAHE settings applied to the image. Combining the 10 CLAHE conditions, 4 contrast levels and 4 orientations gave 160 combinations. The trials were constructed by pairing 160 combinations of key variables with 40 backgrounds. Twenty student observers were asked to detect the orientation of the spiculation in the image. There was a statistically significant improvement in detection performance for spiculations with CLAHE over unenhanced images when the region size was set at 32 with a clip level of 2, and when the region size was set at 32 with a clip level of 4. The selected CLAHE settings should be tested in the clinic with digital mammograms to determine whether detection of spiculations associated with masses detected at mammography can be improved.

Female↗

Implantable contact lens for moderate to high myopia: phase 1 FDA clinical study with 6 month follow-up.

PURPOSE: To assess the short-term safety and efficacy of the implantable contact lens (ICL) to treat moderate to high myopia. SETTING: Phase 1 U.S. Food and Drug Administration clinical study of the ICL conducted at four sites in the United States. METHODS: Ten patients with myopia of 7.00 diopters (D) or greater had implantation of a Staar Surgical ICL and were examined preoperatively (baseline) and 1 day, 1 week, and 1, 3, and 6 months postoperatively. Mean preoperative myopia was 7.75 D (range 7.25 to 9.37 D). RESULTS: Six months postoperatively, 5 of 10 eyes (50%) had an uncorrected visual acuity (UCVA) of 20/20 or better, and all eyes had a UCVA of 20/30 or better. All eyes had a best spectacle-corrected visual acuity (BSCVA) of 20/20 or better and 6 eyes (60%), of 20/15 or better. Six eyes (60%) had an improvement of one or more lines of BSCVA. Mean postoperative spherical equivalent was -0.025 D +/- 0.47 (SD). Eight eyes (80%) were within +/- 0.250 D of emmetropia, and all were within +/- 1.125 D. No intraoperative or postoperative complications or adverse reactions were observed. CONCLUSIONS: The results support the short-term safety, efficacy, and predictability of ICL implantation to treat moderate to high myopia.

Adult↗

Does intensity windowing improve the detection of simulated calcifications in dense mammograms?

This study attempts to determine whether intensity windowing (IW) improves detection of simulated calcifications in dense mammograms. Clusters of five simulated calcifications were embedded in dense mammograms digitized at 50-microns pixels, 12 bits deep. Film images with no windowing applied were compared with film images with nine different window widths and levels applied. A simulated cluster was embedded in a realistic background of dense breast tissue, with the position of the cluster varied. The key variables involved in each trial included the position of the cluster, contrast level of the cluster, and the IW settings applied to the image. Combining the ten IW conditions, four contrast levels and four quadrant positions gave 160 combinations. The trials were constructed by pairing 160 combinations of key variables with 160 backgrounds. The entire experiment consisted of 800 trials. Twenty student observers were asked to detect the quadrant of the image in which the mass was located. There was a statistically significant improvement in detection performance for clusters of calcifications when the window width was set at 1024 with a level of 3328, and when the window width was set at 1024 with a level of 3456. The selected IW settings should be tested in the clinic with digital mammograms to determine whether calcification detection performance can be improved.

Breast Neoplasms↗

Evaluation of a medical ethics consultation service: opinions of patients and health care providers.

PURPOSE: To study the perceived effectiveness of bioethics consultation as evaluated by both professional staff and patients and their families. PATIENTS AND METHODS: An evaluation questionnaire was forwarded to physicians, nurses and patients or family members who were associated with 20 sequential cases referred for ethics consultation during a 2-year period. Respondents were asked to rate the consult as very helpful, somewhat helpful, or not helpful concerning a variety of issues related to the care of the patients. Responses were reviewed for agreement or disagreement between the three sample groups. RESULTS: Ninety-six percent of physicians and 95% of nurses sampled felt that the consult was helpful, compared with only 65% of the patient/family responses. Lack of communication between patients and staff was cited as a problem in all cases in which the consult was deemed unhelpful by patients and family. CONCLUSIONS: Patients or family members and professional staff have different perceptions regarding the value of bioethics consultation. When asked for comments, patients/family members cite lack of communication with professional staff as their primary reason for responding negatively. Earlier mobilization of consultative staff, rigorous training of consultants in techniques of conflict resolution, and education of primary caregivers regarding recognition of communication problems may serve to narrow this perceptual divergence.

Adolescent↗

Long-term (5- to 12-year) follow-up of metal-blade radial keratotomy procedures.

OBJECTIVE: To evaluate the long-term stability of the refractive outcome after metal-blade radial keratotomy procedures. DESIGN: A cohort of 146 patients who underwent 225 consecutive metal-blade radial keratotomy procedures that were performed under a uniform protocol between November 1979 and August 1981 was monitored prospectively, with 64% of the patients followed up for at least 5 years. MAIN OUTCOME MEASURES: Changes in spherical equivalent and changes in average keratometry were evaluated within the following periods: 3 months to 1 year; 1 to 2 years; 2 to between 3 and 4 years (mean, 3.7 years); between 3 and 4 (mean, 3.7 years) to between 5 and 12 years (mean, 8.5 years); and 1 to between 5 and 12 years (mean, 8.5 years). RESULTS: Total mean change in refraction between 1 year and the average of 8.5 years of follow-up was 1.01 diopters (D) (SD, 1.13 D). At 1 year, 31% of the cases were at least 1 D hyperopic, whereas at an average of 8.5 years, 48% were at least 1 D hyperopic. Fifty-four percent of the cases had shifted in the hyperopic direction by 1 D or more. Stepwise regression analysis failed to identify significant predictive factors for the hyperopic shifts. CONCLUSIONS: The trend toward progressive hyperopic shifts within this cohort has continued with time. Other long-term studies have documented similar, although somewhat smaller, hyperopic shifts among both patients treated with metal-blade and patients treated with diamond-blade procedures. Causative factors for the hyperopic shift have not been identified. It remains to be seen if eyes undergoing current, more cautious surgical approaches to radial keratotomy will also experience this phenomenon.

Follow-Up Studies↗

Changing practice patterns in refractive surgery: results of a survey of the American Society of Cataract and Refractive Surgery.

A questionnaire on refractive surgical practice was sent to the entire membership of the American Society of Cataract and Refractive Surgery in 1992. One thousand eight hundred and forty-one (1,841) of the 4,950 members returned the survey for a response rate of 37.2%. The questionnaire was designed to be self-administered and elicited information on types of refractive procedures performed in the survey year and the preceding year, as well as the intent to perform refractive procedures in the future. Surgeons who perform radial keratotomy (RK) increased from 22% in 1991 to 30% in 1992; 45% expected to perform RK in 1993-1994. The following categories of information were requested: characteristics of RK patients, techniques used by the surgeon, characteristics of the surgeon's overall practice, type of RK training, surgical outcome, and prevalence of complications. The results of this survey indicate that the use of RK and astigmatic keratotomy (AK), as well as other refractive procedures, is steadily increasing. Radial keratotomy was mainly performed on patients 20 to 49 years of age who had low to moderate myopia. The majority of surgeons used four to eight radials, centrally directed incisions, and single depth settings. Three quarters of the surveyed RK surgeons used the Casebeer nomogram. The survey results indicated that 42% of surgeons performing photorefractive keratectomy (PRK) did not perform RK or other refractive procedures, suggesting that growth in the practice of PRK following FDA approval may come from both current RK surgeons and novice refractive surgeons.

Adult↗

Small incision surgery with the STAAR Elastimide three-piece posterior chamber intraocular lens.

One hundred twelve patients scheduled for uncomplicated cataract removal were randomly assigned to receive a STAAR Elastimide three-piece foldable intraocular lens inserted through a 4.0 mm incision or a STAAR poly(methyl methacrylate) (PMMA) lens inserted through a 7.0 mm incision. The same surgeon performed all surgeries using identical techniques, except for incision size and number of sutures. Patients receiving Elastimide lenses had significantly better uncorrected visual acuity postoperatively than patients receiving PMMA lenses and also had significantly less keratometric cylinder, surgically induced cylinder (vector method), and refractive cylinder. The Elastimide foldable lens offers the advantages of small incision surgery for patients who require a three-piece lens.

Aged↗

Effect of posterior chamber intraocular lens design and surgical placement on postoperative outcome.

Intraocular lens (IOL) design, optical configuration, and placement have potential effects on postoperative outcome. Laboratory studies have suggested that one-piece, biconvex designs may reduce or delay posterior capsular opacification and that in-the-bag fixation of the posterior chamber IOL may reduce inflammation. To document the clinical significance of IOL design and placement, we conducted a randomized, prospective, clinical trial. Six hundred uncomplicated capsulorhexis and phacoemulsification patients were randomized in a three-factor design to receive an IOL that was one-piece or three-piece, had a biconvex, plano-convex, or laser ridge optic, and was bag-or sulcus-fixated. Treatment differences were related to lens placement. Patients with bag-fixated IOLs had less posterior capsular opacification, fewer YAG laser capsulotomies, a higher percentage of centered lenses, less inflammation, and fewer late posterior capsular striae than those with sulcus-fixated IOLs. In the latter group, patients with three-piece IOLs had fewer posterior capsular striae at three months postoperatively. All six occurrences of haptic loop distortion were in patients with three-piece IOLs. Patients with the one-piece design had less late inflammation than those with the three-piece design. Fewer YAG capsulotomies were necessary at one year in patients with the biconvex design than in those with the plano-convex or laser ridge configurations. Operative complications, endothelial cell loss, and postoperative complications were not IOL-related.

Adult↗

Effect of a superficial and a deep scleral pocket incision on the incidence of hyphema.

Deep tunnel scleral pocket incisions were developed to control surgically induced astigmatism following cataract and intraocular lens implantation surgery. A more superficial, shallow scleral pocket incision was developed to reduce the rate of postoperative hyphema. To test its effectiveness, a randomized prospective clinical study was performed. One hundred twenty-nine eyes of 129 patients were randomized: 66 to receive a deep tunnel pocket and 63 to receive the superficial pocket. In both groups the incision was made 3 mm posterior to the limbus. For the deep pocket cases, a blade setting of 0.27 mm was used and the wound was dissected forward toward the entry site, creating a long, deep, narrow tunnel. For the superficial wound cases, a 0.17 mm blade setting was used and the entire wound was dissected to the edge of the anatomic limbus, creating a thin scleral flap. The left side was then fanned out toward the left with the entry site slightly into clear cornea. At one day after surgery, 22 cases (34%) in the deep pocket group and four cases (6%) in the superficial pocket group had hyphemas. The difference in hyphema rates was statistically significant (P less than .001).

Adult↗

Effect of suture material on postoperative astigmatism.

Two hundred patients were enrolled in a randomized, prospective clinical trial comparing the use of 10-0 nylon, 10-0 polypropylene (Prolene), 11-0 polyester (Mersilene), and 10-0 polyethylene (Novafil) suture materials on the amount and decay curves of surgically induced astigmatism following intraocular lens (IOL) surgery. Patients with Mersilene and nylon sutures had the highest amounts of induced with-the-rule (WTR) cylinder (significantly more than Prolene) at one day after surgery. However, the WTR cylinder decayed rapidly for nylon during the first three months but more slowly for Mersilene because of its lack of stretchability. The Prolene group had the lowest level of induced WTR cylinder at one day, but against-the-rule (ATR) drift occurred, leaving cases with ATR astigmatism by a year. The nylon group had the second highest amount of induced WTR cylinder at one day, which had decayed to ATR cylinder by five months. Between one and two years postoperatively, the nylon group experienced a significant ATR shift. The amount of early induced WTR cylinder seemed to be related to the knot-tying technique and tissue gripping characteristics, whereas the shape of the decay curve was related to the material characteristics of the suture.

Adult↗

Effect of small incision intraocular lens surgery on postoperative inflammation and astigmatism. A study of the AMO SI-18NB small incision lens.

A single center, single surgeon, randomized, prospective clinical trial was performed comparing the effectiveness of small (3.5 mm to 4.0 mm) incision intraocular lens surgery and a larger (6.0 mm) incision in improving uncorrected visual acuity and reducing post-operative inflammation and surgically induced astigmatism. One hundred twelve eligible unilateral cases were randomized to receive a 3.5 mm to 4.0 mm incision with implantation of an Allergan Medical Optics three-piece SI-18NB silicone lens (56 cases) or a 6.0 mm incision with implantation of a three-piece biconvex poly(methyl methacrylate) lens (56 cases). At one day after surgery, significantly (P less than .01) more patients with 3.5 mm incisions had 20/40 or better uncorrected visual acuity than patients with 6.0 mm incisions (45% vs 20%). Forty percent of patients with 6.0 mm incisions vs 14% of patients with 3.5 mm incisions had visual acuities of 20/100 or worse. At one day after surgery, the larger incision group had significantly higher (P less than .01) mean keratometric cylinder (2.28 diopters vs 1.28 diopters in the small incision group). The two groups were comparable by three months. Laser flare/cell meter measurements were taken for each group but showed no significant differences in mean flare or cell measurements between the groups.

Aged↗

Multifocal versus monofocal intraocular lenses. Visual and refractive comparisons.

In a unilateral prospective clinical trial, 77 cases were randomized to receive a 3M multifocal IOL or a conventional monofocal implant. Multifocal cases had better uncorrected near vision than monofocal cases at the two to four month visit. Thirty percent of the multifocal cases had near acuity J1, while only 4% of the monofocal cases had that acuity. Eighty-seven percent of multifocal cases and 71% of monofocal cases had near acuities of J1 to J3. With distance correction in place, 54% of multifocal cases had near acuities of J1 to J2, while only 28% of monofocal cases had comparable acuities (P = .04). There have been no serious postoperative complications in either group.

Cataract Extraction↗

Purification and characterization of an oxygen-insensitive NAD(P)H nitroreductase from Enterobacter cloacae.

The reductive products of several nitroaromatic compounds have been found to be toxic, mutagenic, and carcinogenic. The nitroreductases present in intestinal microflora have been implicated in the biotransformation of these compounds to their deleterious metabolites. A "classical" nitroreductase has been purified from Enterobacter cloacae 587-fold using a protocol which yields approximately 1 mg of purified nitroreductase from 10 liters of cell culture. An analysis of the physical properties of the nitroreductase indicates that the enzyme is active as a monomer with a calculated molecular mass of 27 kDa. FMN has been identified as a required flavin cofactor and is present at a stoichiometry of 0.88 mol of FMN bound/mol of active enzyme. The enzyme was found capable of reducing nitrofurazone under aerobic conditions indicating that the mechanism involves an obligatory two-electron transfer. Thus, this enzyme can be classified as an oxygen-insensitive nitroreductase. The purified nitroreductase can utilize either NADH or NADPH as a source of reducing equivalents and can reduce a variety of nitroaromatic compounds including nitrofurans and nitrobenzenes as well as quinones. Studies in which the rates of nitroreduction for a series of para substituted nitrobenzene derivatives were determined suggest that a linear free energy relationship exists between the rate and the redox midpoint potential of the substrate.

Bacterial Proteins↗