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Biomedical subjects

C Benedict

Publications and source records attributed to C Benedict.

32 records · Page 2Linked to original sources

Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD).

Neuroendocrine activation is known to occur in patients with congestive heart failure, but there is uncertainty as to whether this occurs before or after the presence of overt symptoms. In the Studies of Left Ventricular Dysfunction (SOLVD), a multicenter study of patients with ejection fractions of 35% or less, we compared baseline plasma norepinephrine, plasma renin activity, plasma atrial natriuretic factor, and plasma arginine vasopressin in 56 control subjects, 151 patients with left ventricular dysfunction (no overt heart failure), and 81 patients with overt heart failure before randomization. Median values for plasma norepinephrine (p = 0.0001), plasma atrial natriuretic factor (p less than 0.0001), plasma arginine vasopressin (p = 0.006), and plasma renin activity (p = 0.03) were significantly higher in patients with left ventricular dysfunction than in normal control subjects. Neuroendocrine values were highest in patients with overt heart failure. Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased (p less than 0.05) in patients on diuretic therapy. We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure. Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy.

Arginine Vasopressin↗

Nicotine regulation among heavy and light smokers in a non-stressful environment.

The purpose of this study was to assess nicotine regulation among "heavy" and "light" smokers. Previous studies supporting the nicotine regulation model of smoking behavior have suggested that smokers compensate for a reduction in the amount of nicotine available in their cigarette by altering smoking frequency, puff volume, or other aspects of smoking topography. However, little is known about a smoker's decision to smoke a specific cigarette, and the concurrent changes in their blood nicotine. Manipulation of nicotine levels in the blood could play a critical role in smoking maintenance, by regulating the extent and quality of the CNS effects of smoking. In this study, 24 heavy and light smokers (cotinine above or below 260 ng/ml) smoked high- (1.0 mg) or low- (0.5 mg) dose nicotine cigarettes while watching non-stressful movies. Blood nicotine was assessed before and after smoking a preload and free operant cigarette. The results showed that blood nicotine levels after smoking the free operant cigarette were significantly more consistent (lower standard error) for the heavy smokers, following a low dose, as opposed to a high-dose preload. Light smokers showed a non-significant trend towards being more consistent when the high-dose nicotine preload was used. This suggests that heavy smokers may have maximized their dose of nicotine whenever available nicotine was in relatively short supply (low dose condition). However, light smokers may have minimized their exposure when available nicotine was relatively more plentiful (high dose condition).

Adult↗

Preliminary evaluation of the use of mussel adhesive protein in experimental epikeratoplasty.

We have used a preliminary formulation of a bioadhesive in an experimental model of epikeratoplasty in rabbits. The adhesive, termed mussel adhesive protein (MAP), is a repeating decapeptide polymer that is the natural adhesive substance produced by the common blue mussel (Mytilus edulis) and is used here in conjunction with an enzymatic cross-linking agent. This study marked the first in vivo use of this material in adhering ophthalmic tissue planes. We used a simplified epikeratoplasty technique highlighted by freehand dissection of donor lenticules and host keratotomies. Approximately 10 microL of a combination of MAP and the cross-linking agent was applied directly to the host cornea and the donor lenticules were secured into the keratotomies using eight interrupted 10-0 nylon sutures. All of the sutures were removed 72 hours postoperatively. Eleven of the 15 animals retained their epikeratoplasty lenticules throughout the entire postoperative period. Four animals had initially intact lenticules that sloughed within the first postoperative week; this sloughing, we believe, was attributable to difficulties in tucking irregularly thickened lenticule edges into the keratotomy. In control animals that had lenticules secured with sutures alone, suture removal at 72 hours consistently produced immediate lenticule sloughing. Clinical examinations and histopathologic studies disclosed no untoward effects of the adhesive on the donor or host corneal tissue. We believe that this preliminary study indicates a potential adjunctive role for MAP in epikeratoplasty.

Animals↗

Electrophysiological monitoring during acoustic neuroma and other posterior fossa surgery.

Techniques used to monitor the function of the seventh and eighth cranial nerves during acoustic neuroma and other posterior fossa surgery are reviewed. The auditory brainstem response (ABR), electrocochleogram (ECochG) and direct recording from the auditory nerve (CNAP) were compared. The best technique is the ECochG, although in many cases, the CNAP should be used as a back-up technique. The CNAP is especially useful for the identification of the auditory nerve. Both can provide real-time feedback on the physiological integrity of the auditory nerve. The ABR may be helpful in monitoring brainstem function. For some procedures, optimal monitoring requires the combined recording of all three techniques. Monopolar constant-voltage intracranial stimulation of the facial nerve is helpful for the identification and preservation of the facial nerve. Audio monitoring of spontaneous electromyographic activity provides real-time feedback on the effect of surgical manipulation of the nerve. Monitoring of ephaptic transmission in the facial nerve during microvascular decompression for hemifacial spasm aids in the identification of the offending vessel.

Action Potentials↗

Determination of aldosterone secretion rate utilizing mixed mode and high performance liquid chromatography.

A simpler method for determining aldosterone secretion rate (ASR) has several applications. High performance liquid chromatography (HPLC) has several advantages over traditional chromatographic methods for purification to constant specific activity of aldosterone liberated from its 18-glucuronide by acid hydrolysis. We found it necessary to introduce several modifications to remove urochromes before HPLC. Two methods for determining ASR were developed. With Method A a more traditional initial procedure was followed, and Sephadex LH-20 chromatography allowed removal of considerable urochromes before HPLC. However, aldosterone recovery was improved with Method B, which employed several bonded phase silica derivatives (Sepralytes) and a PBE 94 column to remove urochromes before HPLC. With this procedure the Sephadex LH-20 chromatography was not required. Aldosterone purification to constant specific activity was achieved by HPLC on a diol column with a normal phase system, and quantification was performed by RIA. ASR determinations were equivalent with both methods. This methodology should be applicable to other steroid secretory rate determinations and to applications involving purification of steroid conjugates.

Aldosterone↗

Inhibition of arabinose 5-phosphate isomerase. An approach to the inhibition of bacterial lipopolysaccharide biosynthesis.

Arabinose 5-phosphate ( A5P ) isomerase is a key enzyme in the biosynthesis of lipopolysaccharide, an essential component of the outer membrane of Gram-negative bacteria. The mechanism of the isomerase is envisioned to involve an enediol intermediate. A series of compounds, which are analogues of the substrates or intermediate, were tested as inhibitors of A5P isomerase with the belief that a good inhibitor would stop bacterial growth or render the cells more susceptible to other antibiotics or natural defenses. In a series of phosphorylated sugars, the order of isomerase inhibitory activity was as follows: aldonic acids greater than alditols greater than aldoses. Nonphosphorylated sugars were much less inhibitory. The best inhibitor was erythronic acid 4-phosphate (54), which had Km/Ki = 29. None of the compounds displayed antibacterial activity in vitro.

Aldose-Ketose Isomerases↗

Neurohormonal changes after implantation of a left ventricular assist system.

In patients with left ventricular dysfunction, neurohormonal levels are valuable indicators of the severity of heart disease and prognosis. For patients with severe left ventricular dysfunction, left ventricular assist systems (LVAS) are effective as short-term bridges to heart transplantation and are currently being investigated for long-term use. Unknown, however, are the effects of mechanical unloading of the left ventricle on neurohormone levels during the initial weeks after LVAS implantation, and whether these changes are similar to the neurohormonal level decreases observed after cardiac transplantation. This study was undertaken to determine the effect of LVAS support on plasma norepinephrine (PNE) levels during the initial weeks after device implantation. The PNE levels in five consecutive patients with left ventricular dysfunction were measured within 1 week after LVAS implantation and every week thereafter for 5 weeks. Significant decreases in PNE levels were observed after 3 weeks of LVAS support. After 5 weeks of LVAS support, PNE levels had decreased to near normal. For patients with severe left ventricular dysfunction, the improved prognosis after LVAS support may be due in part to the normalization of neurohormonal levels. The findings indicate that PNE levels may be of value in determining whether a patient can be weaned from LVAS support.

Aged↗

Differential diagnosis of oncocytic lesions of the breast and thyroid utilizing a semiquantitative approach.

OBJECTIVE: To assess whether a light microscopic, semiquantitative approach could reliably distinguish between benign nonneoplastic, benign neoplastic and malignant oncocytic lesions of the breast and thyroid. STUDY DESIGN: Alcohol-fixed, Papanicolaou-stained fine needle aspiration smears of histologically proven goiter and chronic thyroiditis (18 cases), Hürthle cell adenomas (7 cases), Hürthle cell carcinomas (6 cases), fibrocystic disease (17 cases), papillomas and papillomatosis (7 cases) and apocrine carcinomas (6 cases) were rated by three independent observers using the following 10 cytologic criteria: cellularity, nuclear-cytoplasmic ratio, multinucleation, nuclear size, nuclear shape, anisonucleosis, multinucleolation, nucleolar-nuclear ratio, nucleolar size and nucleolar shape. Each of these 10 cytologic criteria was rated using a 1-3 scale. The scores for all 10 features were summed to give a total score for each case. The total scores were statistically analyzed to determine the validity and reproducibility of the summed criteria. RESULTS: The summed criteria of the total scores were reproducible between the three observers, with standard deviations ranging from 1.36 to 2.88 for thyroid and 1.72 to 2.00 for breast oncocytic lesions. The ability of the total scores to differentiate benign from malignant oncocytic lesions of the breast and thyroid was confirmed by a positive predictive value for malignancy of 67% for thyroid and 72% for breast and a negative predictive value for malignancy of 100% for nonneoplastic oncocytic lesions and > 90% for benign oncocytic neoplasms in both. The Kruskal-Wallis test revealed that the total scores were able to distinguish three diagnostic categories of nonneoplastic, benign neoplastic and malignant oncocytic breast and thyroid lesions, with P < .005. CONCLUSION: Without the expenditures of additional time, costs or materials, this semiquantitative approach compared favorably with contemporary morphometric studies involving the differential diagnosis of oncocytic cell pathology in fine needle aspiration cytology.

Breast Neoplasms↗