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Biomedical subjects

R Hamilton

Publications and source records attributed to R Hamilton.

At least 37 records · Page 2Linked to original sources
PubMed1988

Identification of etoposide glucuronide as a major metabolite of etoposide in the rat and rabbit.

Isolated livers from male Sprague-Dawley rats were perfused at 20 ml/min for 3 h at 37 degrees C with 100 ml of an oxygenated, recirculating solution of 20% rat blood in Krebs bicarbonate buffer containing 20 micrograms/ml [3H]etoposide. Ninety % of administered radioactivity was eliminated in bile over a 3-h collection period. The clearance of etoposide was 3.56 ml/min indicating that, in the rat, it is not highly extracted. Its clearance is, therefore, independent of hepatic blood flow. Etoposide was both excreted into the bile and metabolized by the liver. Perfusate and bile samples analyzed by reverse-phase high-performance liquid chromatography techniques were found to contain three peaks of radioactivity. Positive and negative ion fast atom bombardment mass spectrometry identified the first two peaks as etoposide glucuronides and the third peak as parent drug. Following the i.v. administration of etoposide to rabbits, etoposide glucuronide was also identified in rabbit urine. The recovery of etoposide both from rabbit urine and rat bile was increased by preincubation with glucuronidase. However, the glucuronides were relatively resistant to the action of glucuronidase and showed varying sensitivity to the type of glucuronidase and the reaction conditions used. These studies document the presence of etoposide glucuronide as an etoposide metabolite in two mammalian species and suggest that previous clinical studies using beta-glucuronidase to quantitate glucuronide formation may have underestimated this metabolite due to its relative resistance to some glucuronidase preparations.

Animals↗
PubMed1988

Successful localization of parathyroid adenomas by magnetic resonance imaging.

Exploration of the neck for primary hyperparathyroidism is facilitated if the parathyroid glands can be localized preoperatively. Magnetic resonance imaging is a noninvasive and relatively safe procedure that is capable of distinguishing and differentiating small soft-tissue structures. Ten patients with primary hyperparathyroidism underwent preoperative diagnostic magnetic resonance imaging followed by cervical exploration. In 9 of these patients (90 percent), imaging correctly predicted the location of a single enlarged parathyroid gland, and in one patient the findings were misleading. All 10 patients proved to have single adenomas in orthotopic locations. Based on this early experience, magnetic resonance imaging appears to be a promising technique for preoperative localization of an enlarged parathyroid gland.

Adenoma↗
PubMed1988

A comparison of local recurrence and resection margins for stage I primary cutaneous malignant melanomas.

A retrospective review of 552 patients with clinical stage I primary cutaneous malignant melanomas was undertaken comparing margins of resection and local recurrence between 1966 and 1981. The overall local recurrence rate was 8 per 552 (1.45 percent). We observed no instances of local recurrence in lesions less than 1.40 mm thick with resection margins of at least 1 cm. A comparison of resection margins greater than 2 cm versus less than 2 cm for lesions less than 1.00 mm thick showed no difference at the 0.05 level of significance for local recurrence (0 per 228 versus 2 per 154; 1.3 percent) or survival. While narrower margins of resection for thinner, low-risk stage I malignant melanomas appear safe, the exact minimum margin of resection needed to satisfy both oncologic and cosmetic considerations, whether 1 or 2 cm, will need to be determined by a large prospective, randomized study.

Adolescent↗
PubMed1987

Compilation and comparison of the sequence context around the AUG startcodons in Saccharomyces cerevisiae mRNAs.

The nucleotide sequence of the translation initiation regions of 96 Saccharomyces cerevisiae mRNAs was compiled and compared. The entire 5' untranslated sequence of most mRNAs is very rich in A-residues. G-residues are underrepresented in the untranslated region. The AUG startcodon context appeared to be distinctly different from that of animal mRNAs, although an A-residue at -3 also occurs very frequently (81 percent) in yeast mRNAs. The prevailing codon 3' adjacent to the AUG is the UCU serine codon. All these features are more extreme in the highly expressed genes. Fifty percent of all highly expressed genes use the UCU serine codon as second triplet. In this group G-residues are completely absent in the 7 bases preceding the startcodon and an A-residue occurs at position -1 and -3 at a frequency of 89 percent and 100 percent, respectively. The abundance of A-residues throughout the leader suggests that unstructured mRNA is required for efficient translation initiation in yeast. The consensus sequence for the AUG context in highly expressed genes can be summarized as follows: (Sequence: see text).

Base Sequence↗
PubMed1987

Management of cutaneous melanomas of the female breast.

Primary melanomas of the skin of the breast are uncommon lesions. Fifty-four patients were surgically treated for this lesion during a 13-year period, accounting for 3.8 percent of a total of 1431 patients with cutaneous melanoma. Nineteen patients were female and 35 were male. Most recently, in patients with high-risk lesions, such as those exhibiting an aggressive vertical growth phase or a Clark level IV or V, attempts at curative resection have utilized wide and deep excision to the level of the pectoralis fascia with axillary lymph node dissection in selected cases. Reconstruction of the significant breast deficit in five female patients utilized the latissimus dorsi myocutaneous flap. This technique results in an improved aesthetic appearance when compared to primary closure or skin grafting. Donor-site morbidity is minimal. Long-term cancer surveillance is not impeded, and all five patients expressed satisfaction with the reconstruction. Four of the five female patients are currently alive with no evidence of disease at a mean follow-up of 55 months after definitive therapy.

Adolescent↗
PubMed1987

Abnormal parathyroid glands: high-resolution MR imaging.

High-resolution magnetic resonance (MR) images of the neck were obtained in 23 patients with hyperparathyroidism. Surgical confirmation was available in all cases. MR imaging allowed accurate localization of 14 of 17 parathyroid adenomas, two of two parathyroid carcinomas, and five of eight hyperplastic glands, the latter from three patients. MR depicted nine of 11 (82%) abnormal glands that were 0.5-1.0 cm in size and 12 of 14 (85.7%) glands larger than 1 cm in diameter. In all but one case, abnormal glands had signal intensity greater than or equal to that of fat on spin-echo images with long repetition time and echo time. Parathyroid adenomas, carcinomas, and hyperplasia could not be distinguished from each other. The overall sensitivity and specificity of MR imaging in the detection of parathyroid abnormalities was 77.8% and 95.4% respectively, resulting in an accuracy of 90.2%. This compares favorably with other imaging modalities.

Adenoma↗
PubMed1986

Chronic caffeine administration exacerbates renovascular, but not genetic, hypertension in rats.

The purpose of this study was to determine whether or not caffeine would exacerbate renovascular hypertension. Therefore, we examined the effects of chronic caffeine administration on arterial blood pressure in rats subjected to either unilateral renal artery clipping (2K-1C rats) or sham-operation. Animals in each group were randomly assigned to receive either 0.1% caffeine in their drinking water or normal drinking water, and systolic blood pressure was monitored for 6 wk. Caffeine markedly exacerbated the severity of hypertension in 2K-1C rats and caused histological changes consistent with malignant hypertension. 6 wk after surgery, systolic blood pressure, plasma renin activity, and creatinine clearance in control 2K-1C rats were 169 +/- 5 mmHg (mean +/- SEM), 4.4 +/- 0.5 ng AI X ml-1 X h-1, and 2.9 +/- 0.2 ml/min, respectively; as compared with 219 +/- 4 mmHg, 31.8 +/- 7.8 ng AI X ml-1 X h-1, and 1.4 +/- 0.3 ml/min, respectively, in 2K-1C rats receiving caffeine (all values were significantly different compared with control 2K-1C). Chronic caffeine administration did not alter systolic blood pressure, plasma renin activity, or creatinine clearance in sham-operated rats or spontaneously hypertensive rats. Chronic treatment with enalapril (a converting enzyme inhibitor) prevented the development of hypertension in control 2K-1C rats and caffeine-treated 2K-1C rats; however, withdrawal of enalapril precipitated a rapid rise in systolic blood pressure in caffeine-treated 2K-1C rats, but not in control 2K-1C rats. These experiments indicate that caffeine specifically exacerbates experimental renovascular hypertension and might worsen the hypertensive process in patients with renovascular hypertension.

Animals↗
PubMed1986

Identification of circulating parasite antigen in patients with bancroftian filariasis.

Because many cases of lymphatic filariasis cannot be diagnosed either clinically or by immunodiagnostic test based on antibody detection, recent efforts have been more directed towards developing methods for detecting parasite antigen in the blood or urine. Using a solid phase (Sepharose 4B) two-site immunoradiometric assay (IRMA) employing hyperimmune rabbit antifilarial antisera, we have previously shown (Hamilton et al., 1984) that essentially all cases of patent (ie. microfilaremic) infection in patients with bancroftian filariasis can be detected by this semi-quantitative assay as well as some individuals with amicrofilaremic (i.e., 'cryptic') infection. The present communication reports the results of studies that identify a prominent circulating antigen detected by this IRMA in sera from patients with microfilaremia. The antigen was eluted from Sepharose-bound rabbit polyclonal antiserum that had been reacted with known antigen positive sera. It was run in SDS-PAGE, blotted to nitrocellulose paper and identified autoradiographically using 125I-labelled rabbit antifilarial antiserum. Its high molecular weight (approximately 200 kD), stability to acid and boiling, and sensitivity to pronase and periodate suggest its being a glycoprotein. Isolation of this antigen will permit the development of specific reagents (such as monoclonal antibodies) which should enhance both the sensitivity and utility of the currently available antigen detection systems.

Adolescent↗
PubMed1986

Potassium.

Potassium homeostasis is dependent on many physiologic and metabolic factors. Potassium level testing by the clinical laboratory can aid the emergency physician in planning treatment in suspected cases of potassium depletion or excess. Familiarization with indications for ordering tests of potassium level and correct interpretation of test results is essential for appropriate patient care.

Adult↗
PubMed1985

The role of lymph node dissection for clinical stage I malignant melanoma of intermediate thickness (1.51-3.99 mm).

The survival times of patients who had an elective regional lymph node dissection was compared with that of those who did not undergo the procedure in a database of 72 patients with clinical Stage I melanoma of intermediate thickness (1.51-3.99 mm). All of the patients had been followed for 5 years or longer or until death. No significant differences were found in other reported prognostic factors, suggesting that the two groups were comparable. By multivariate analysis, a low mitotic rate, intermediate patient age, and the presence of an infiltrative lymphocytic response were found to be associated with favorable survival. There did not appear to be any association of elective regional lymph node dissection with survival; and it was concluded that such therapy should not be regarded as "standard" for clinical Stage I melanoma of intermediate thickness.

Actuarial Analysis↗
PubMed1985

Laser Doppler surveillance of the circulation of free flaps and replanted digits.

In a series of 40 clinical free flaps and replantations the laser doppler technique has been used successfully for postoperative surveillance of circulation. A uniform flow pattern was obtained from all uncomplicated cases contrasting to the flow pattern seen in cases with thrombotic complication. The laser doppler continuously records flow of the microcirculation and is able to monitor blood flow in all types of free tissue transfer presently used as well as replantations. The laser doppler has effectively diagnosed two arterial thromboses with a characteristic flow pattern. It can distinguish venous from arterial occlusion. It can record flow in skin flaps which are difficult to judge clinically and in buried flaps, where no clinical observations are possible. The laser doppler should be used in conjunction with routine clinical observations.

Adolescent↗
PubMed1985

Antitrust aspects of exclusive contracts in medical imaging.

Exclusive contracts between radiologists and hospitals may be more frequently scrutinized for antitrust violations because of the Hyde v Jefferson Parish Hospital District No. 2 case. In the Hyde case, the lower court decided antitrust law had been violated, and it was the first antitrust case about exclusive medical contracts to be reviewed by the U.S. Supreme Court. The case is a precedent for considering similar circumstances according to traditional business antitrust analyses such as per se violations, tying arrangements, group boycott, and market foreclosure. Areas that may be scrutinized for anticompetitiveness include hospital privileges when radiologists have exclusive contracts with the community's only hospital or provide services unique within an area, and physicians' access to scarce resources (e.g., computed tomography [CT], magnetic resonance [MR] imaging). Radiologists must understand antitrust implications of their hospital contracts; examine the terms of staff appointment, bylaws, and rights; and be able to guide their attorneys through contract negotiations.

Contract Services↗