Functional assessment of the fetal heart: a review.

The purpose of this review is to evaluate the current modalities available for the assessment of fetal cardiac function. The unique anatomy and physiology of the fetal circulation are described, with reference to the difference between in-utero and ex-utero life. M-mode, early/atrial ratio, myocardial performance index, three-dimensional and four-dimensional ultrasound, tissue Doppler including strain and strain rate, speckle tracking, magnetic resonance imaging and venous flow assessment are described. The modalities are analyzed from the perspective of the clinician and certain questions are posed. Does the modality assess systolic function, diastolic function or both? Is it applicable to both ventricles? Does it require extensive post-processing or additional hardware, or does it make use of technology already available to the average practitioner? The reproducibility and reliability of the techniques are evaluated, with reference to their utility in clinical decision-making. Finally, directions for future research are proposed.

The FEMA GRAS assessment of aliphatic and aromatic terpene hydrocarbons used as flavor ingredients.

This publication is the thirteenth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Since then, the number of flavoring substances has grown to more than 2600 substances. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of aliphatic and aromatic terpene hydrocarbons as flavoring ingredients are evaluated. The group of aliphatic and aromatic terpene hydrocarbons was reaffirmed as GRAS (GRASr) based, in part, on their self-limiting properties as flavoring substances in food; their rapid absorption, metabolic detoxication, and excretion in humans and other animals; their low level of flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic and chronic studies and the lack of significant genotoxic potential.

The FEMA GRAS assessment of alpha,beta-unsaturated aldehydes and related substances used as flavor ingredients.

This publication is the 12th in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Since then, the number of flavoring substances has grown to more than 2200 chemically-defined substances. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, toxicodynamics and toxicology. Scientific data relevant to the safety evaluation for the use of aliphatic, linear alpha,beta-unsaturated aldehydes and structurally related substances as flavoring ingredients are evaluated. The group of substances was reaffirmed as GRAS (GRASr) based, in part, on their self-limiting properties as flavoring substances in food; their low level of flavor use; the rapid absorption and metabolism of low in vivo concentrations by well-recognized biochemical pathways; adequate metabolic detoxication at much higher levels of exposure in humans and animals; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic and chronic studies. While some of the compounds described here have exhibited positive in vitro genotoxicity results, evidence of in vivo genotoxicity and carcinogenicity occurs only under conditions in which animals are repeatedly and directly exposed to high irritating concentrations of the aldehyde. These conditions are not relevant to humans who consume alpha,beta-unsaturated aldehydes as flavor ingredients at low concentrations distributed in a food or beverage matrix.

The FEMA GRAS assessment of aromatic substituted secondary alcohols, ketones, and related esters used as flavor ingredients.

This publication is the 11th in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. The list of GRAS substances has now grown to more than 2100 substances. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. In this monograph, a detailed interpretation is presented on the renal carcinogenic potential of the aromatic secondary alcohol alpha-methylbenzyl alcohol, aromatic ketone benzophenone, and corresponding alcohol benzhydrol. The relevance of these effects to the flavor use of these substances is also discussed. The group of aromatic substituted secondary alcohols, ketones, and related esters was reaffirmed as GRAS (GRASr) based, in part, on their rapid absorption, metabolic detoxication, and excretion in humans and other animals; their low level of flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic and chronic studies and the lack of significant genotoxic and mutagenic potential.

The FEMA GRAS assessment of phenethyl alcohol, aldehyde, acid, and related acetals and esters used as flavor ingredients.

This publication is the ninth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of phenethyl alcohol, aldehyde, acid, and related acetals and esters as flavoring ingredients is evaluated. The group of phenethylalcohol, aldehyde, acid, and related acetals and esters was reaffirmed as GRAS (GRASr) based, in part, on their self-limiting properties as flavoring substances in food, their rapid absorption, metabolic detoxication, and excretion in humans and other animals, their low level of flavor use, the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic and chronic studies and the lack of significant genotoxic and mutagenic potential. This evidence of safety is supported by the fact that the intake of phenethyl alcohol, aldehyde, acid, and related acetals and esters as natural components of traditional foods is greater than their intake as intentionally added flavoring substances.

The FEMA GRAS assessment of benzyl derivatives used as flavor ingredients.

This publication is the eighth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of benzyl derivatives as flavoring ingredients is evaluated. The group of benzyl derivatives was reaffirmed as GRAS (GRASr) based, in part, on their self-limiting properties as flavoring substances in food; their rapid absorption, metabolic detoxication, and excretion in humans and other animals, their low level of flavor use, the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic and chronic studies and the lack of significant genotoxic and mutagenic potential. This evidence of safety is supported by the fact that the intake of benzyl derivatives as natural components of traditional foods is greater than their intake as intentionally added flavoring substances.

The FEMA GRAS assessment of hydroxy- and alkoxy-substituted benzyl derivatives used as flavor ingredients.

This publication is the ninth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of hydroxy- and alkoxy-substituted benzyl derivatives as flavoring ingredients is evaluated. The group of hydroxy- and alkoxy-benzyl derivatives was reaffirmed as GRAS (GRASr) based, in part, on their self-limiting properties as flavoring substances in food; their rapid absorption, metabolic detoxication, and excretion in humans and other animals; their low level of flavor use; the wide margins of safety between the conservative estimates of intake and the no-observed-adverse effect levels determined from subchronic and chronic studies and the lack of significant genotoxic and mutagenic potential. This evidence of safety is supported by the fact that the intake of hydroxy- and alkoxy-substituted benzyl derivatives as natural components of traditional foods is greater than their intake as intentionally added flavoring substances.

Implications of apoptosis for toxicity, carcinogenicity, and risk assessment: fumonisin B(1) as an example.

The rates of cell proliferation and cell loss in conjunction with the differentiation status of a tissue are among the many factors contributing to carcinogenesis. Nongenotoxic (non-DNA reactive) chemicals may affect this balance by increasing proliferation through direct mitogenesis or through a regenerative response following loss of cells through cytotoxic (oncotic) or apoptotic necrosis. In a recent NTP study in Fischer rats and B6C3F(1) mice, the mycotoxin fumonisin B(1) caused renal carcinomas in male rats and liver cancer in female mice. In an earlier study in male BD-IX rats, fumonisin B(1) caused hepatic toxicity and hepatocellular carcinomas. An early effect of fumonisin B(1) exposure in these target organs is apoptosis. However, there is also some evidence of oncotic necrosis following fumonisin B(1) administration, especially in the liver. Induction of apoptosis may be a consequence of ceramide synthase inhibition and disruption of sphingolipid metabolism by fumonisin B(1). Fumonisin B(1) is not genotoxic in bacterial mutagenesis screens or in the rat liver unscheduled DNA-synthesis assay. Fumonisin B(1) may be the first example of an apparently nongenotoxic (non-DNA reactive) agent producing tumors through a mode of action involving apoptotic necrosis, atrophy, and consequent regeneration.

Cell proliferation in the bladder and implications for cancer risk assessment.

Chemicals can increase carcinogenic risk by either directly damaging DNA or increasing cell replication or they can do both. These effects have different implications for a biologically-based extrapolation from rodent bioassays to humans. 2-Acetylaminofluorene (2-AAF) administered at low doses to mice for a lifetime has a different dose-response for the liver (approximately linear) compared to the urinary bladder (apparent no effect dose of 45 ppm with a sigmoidal dose response at 60-150 ppm), which can be explained if carcinogen metabolism, DNA adduct formation and cell proliferation effects are considered. In contrast to 2-AAF and other genotoxic chemicals, chemicals which form calculi in the urine do not generally damage DNA directly but increase cell proliferation dramatically by eroding the bladder surface, leading to regenerative hyperplasia. This occurs only at doses at which calculi form; lower doses do not produce calculi and, therefore, do not increase cell proliferation or cause tumors. Extrapolation to humans from the rodent bioassay should be dependent on dose requirements for formation of calculi rather than any type of statistical extrapolation to lower doses. Saccharin and other sodium salts administered at high doses to rats also produce bladder cancer by increasing cell proliferation. These salts do not affect mice, hamsters, guinea pig or monkeys. Based on dose and mechanistic considerations, saccharin and these other sodium salts are unlikely to be human carcinogens. Extrapolation to possible human cancer risk requires biological determinations rather than simply using statistical formulations.

The initial worcester experience with laparoscopic hysterectomy.

STUDY OBJECTIVE: To examine three community hospital's experience with the first 108 attempted laparoscopic hysterectomies. DESIGN: Retrospective analysis of hospital and office charts using a standardized data-collection sheet. SETTING: All procedures were performed at the Medical Center of Central Massachusetts, St. Vincent's Hospital, or the University of Massachusetts Medical School, Worcester, Massachusetts. PATIENTS: The first 108 patients to have a laparoscopic hysterectomy attempted. Ninety procedures were completed successfully. MEASUREMENTS AND MAIN RESULTS: Areas that were analyzed were indications for surgery, type of laparoscopic hysterectomy, surgeons' instrument preference, failure to complete the operation, complications, and relative cost. Surgical indications, patient demographics, and complication rates were comparable with those unpublished papers. However, our data showed no improvement in estimated blood loss or operating room time with increased operator experience. Review of pathology reports indicated no cases in which an unsuspected malignancy was encountered. CONCLUSIONS: Laparoscopic hysterectomy can be performed safely and successfully by generalists in obstetrics and gynecology. Additional study is required to know whether variables such as operating room time and expense will improve as this procedure is increasingly performed by generalists rather than specialists.

Laparoscopic colorectal surgery: a prospective assessment and current perspective.

Between August 1991 and June 1993, 74 laparoscopic and laparoscopically assisted colonic and rectal operations were performed. A variety of procedures were carried out including 32 total abdominal colectomies (group 1), 32 segmental resections (group 2) and ten constructions of a diverting stoma without formal resection (group 3). Indications for surgery were mucosal ulcerative colitis in 20 patients, carcinoma in 12, polyposis in six, Crohn's disease in seven and other conditions in the remaining 29. The 74 comprised 42 male and 32 female patients of mean age 45 (range 12-88) years. The median (range) duration of the procedure was 3.0 (1.0-6.5) h for the entire group, 3.9 (2.5-6.5) h for group 1, 2.9 (1.5-5.5) h for group 2 and 1.8 (1.0-2.5) h for group 3. The median (range) length of ileus was 3.0 (2-7) days overall; respective times for groups 1-3 were 3.5 (2-7), 3.0 (2-7) and 2.0 (1-4) days. The median (range) length of hospitalization was 7.0 (2-40) days, 8.1 (4-19) days in group 1, 7.0 (4-20) days in group 2 and 6.0 (2-40) days in group 3. Ten patients (14 per cent) developed intraoperative and 15 (20 per cent) postoperative complications; there were no deaths. These results failed to confirm any significant advantages of laparoscopic or laparoscopically assisted colorectal surgery. Specifically, neither the operating time, nor length of ileus, nor length of hospitalization was improved over standard procedures. Advances in technology and surgical technique may improve such findings in the future.

Development of a postoperative self-assessment form.

This paper describes a patient self-assessment form developed for use in a research study examining early discharge and transitional nursing follow-up care for women with abdominal hysterectomy. Transitional care nursing involves preparation for an early discharge from the hospital and nursing follow-up for convalescence at home through an 8-week recovery period. The goal of transitional care is to assist the client in regaining her preoperative level of self-care. This article will include a brief overview of the ongoing research study, a description of the role of the clinical nurse specialist (CNS) in transitional care, and the use of the self-assessment form. The form is applicable to numerous clinical settings.

Developing a program grant for use in model testing.

Early discharge is becoming a practice as well as a goal for the acute care institution. It is essential that nursing investigate the effects of this shift in the care delivery site from the acute care institution to the home and community. Brooten et al. describe a research model designed to do just that. Transitional care, as this team calls it, may soon become familiar jargon in community health care.

The field dependence of NMR imaging. I. Laboratory assessment of signal-to-noise ratio and power deposition.

A method is proposed for measuring on the bench the NMR signal-to-noise ratio of rf probes, (over the range 1-100 MHz) and also the power deposited in patients during the imaging experiment. The technique is based on the principle of reciprocity, in that a direct relationship exists between the magnetic field generated (upon transmission) by a matched probe coil and the signal-to-noise ratio delivered by the same coil when used as a receiver. The construction and use of a calibrated sense coil for measuring the field is described, and the precautions and theory necessary for accurate measurement and understanding are outlined. Finally, the method is verified by comparison with a direct spectral measure of sensitivity obtained from a small doped water sample placed in NMR imaging equipment.