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Biomedical subjects

B Kramer

Publications and source records attributed to B Kramer.

At least 91 records · Page 5Linked to original sources

Exogenous gonadotropin administration affects the glycocalyx of rat endometrial epithelial cells during the period of implantation.

PURPOSE: Exogenous gonadotropins which cause superovulation are known to effect endometrial morphology, including the glycocalyx of surface epithelial cells. Certain of the carbohydrates in the glycocalyx of surface epithelial cells may be involved in the attachment and implantation of the blastocyst. METHODS: The effect of exogenous gonadotropins on specific carbohydrates in the glycocalyx of the rat endometrium around the time of implantation was investigated. Lectin-avidin-biotin-ferritin cytochemistry was used to ascertain which carbohydrates were affected. The lectins soybean agglutinin, fucose binding protein and wheat germ agglutinin were used. RESULTS: Statistically significantly less lectin was associated with the apical membrane of surface epithelial cells of animals following hyperstimulation than in noninjected pregnant animals. CONCLUSIONS: The reduction in the carbohydrates contributes to a reduced receptivity of the endometrium for the blastocyst.

Animals↗

Calculation of the circular dichroism spectrum of cyclo-(L-tyr-L-tyr) based on a molecular dynamics simulation.

Theoretical calculations of CD spectra have generally assumed a single conformation, or a small number of conformers with Boltzmann averaging. Solvent effects on both the conformation and the CD have been neglected. In this work, we have calculated the CD spectrum of cyclo(L-Tyr-L-Tyr) in aqueous solution, taking dynamics and solvation into account. Starting geometries with chi 1 approximately 300 degrees or 60 degrees for both Tyr side chains were derived from MNDO/MOPAC, followed by energy minimization using GROMOS. After addition of 368 water molecules, the system was simulated for 1000 ps at 300 K using GROMOS. In addition to the starting conformer, two other conformers were observed during each simulation. However, each trajectory gave a distinct set of conformers. Rotational strengths were calculated for the cyclic dipeptide at each ps along the trajectories, using the matrix method. The CD spectra calculated from these rotational strengths were averaged over the trajectories. Agreement is very good for the strong negative band near 200 nm, while for the lower energy bands (near 230 and 280 nm), the signs are correct, but the magnitudes are too low. The spectrum calculated from a Boltzmann-weighted average over the in vacuo MNDO/MOPAC conformers was in poor agreement with experiment. Although the solvent did not significantly affect the rotational strength calculated for a given conformer, it is essential to include the solvent in the MD simulations because it affects the relative energies of the conformers and promotes transitions among them.

Chemical Phenomena↗

Comparative pharmacokinetics and pharmacodynamics of loop diuretics in renal failure.

Loop diuretics increase the fractional excretion of volume, sodium, potassium, chloride and calcium in all stages of renal failure, and their potency is directly correlated with these excretory activities. Tubular secretion of loop diuretics in renal failure is impaired both by reduced renal blood flow and by reduced activity of the tubular carrier system. For these reasons, high concentrations of diuretics in the peritubular capillaries are necessary to guarantee delivery of sufficient drug to their site of action in the ascending limb of the loop of Henle. Piretanide and furosemide have a constant extrarenal elimination and thus accumulate in renal failure. Decreased renal excretion of bumetanide is compensated by hepatic elimination and hence bumetanide does not accumulate. Elimination of torasemide is also independent of its renal excretion. Thus in renal failure, torasemide is the only loop diuretic in which the plasma concentration is strictly dose dependent. Loop diuretics follow a number of different metabolic pathways, but this may not be clinically relevant.

Diuretics↗

Overview of U.S. National Cancer Institute (USNCI) chemoprevention research.

The National Cancer Institute's (NCI) chemoprevention plan employs a strategy of basic and epidemiologic studies, followed by a structured preclinical process to bring chemopreventive agents into clinical testing. The field of chemoprevention is progressing rapidly and has reached the point where a coordinated international approach for large-scale trials would be useful. At present, NCI is sponsoring nine large trials (over $1 million per year per trial); in addition, nine agents are in phase I or II clinical testing. A number of these agents should be ready soon for phase III testing. Resources required for large-scale trials compel greater attention to efficient trial design, concept development and review, priority setting, management, budgeting, and collaboration.

Antineoplastic Agents↗

Voda guiding catheter is superior to amplatz guiding catheter for performing left circumflex PTCA.

Amplatz guiding catheters have traditionally been recommended for performing Left Circumflex PTCA because of their enhanced support. The Voda (Scimed Inc.) design guiding catheter may provide similar support for the left coronary artery, particularly the left circumflex, with less catheter manipulation. We prospectively randomized 40 patients to either Amplatz or Voda guiding catheters to compare ease of use and observed that a Voda design guiding catheter has more favorable characteristics for use without sacrificing support.

Aged↗

A phase II study of continuous infusion 5-fluorouracil and leucovorin with weekly cisplatin in metastatic colorectal carcinoma.

BACKGROUND: Prolonged infusional 5-fluorouracil (5-FU) and bolus 5-FU modulated by leucovorin are associated with higher response rates than bolus 5-FU alone. Cisplatin enhances 5-FU cytotoxicity in some preclinical models. METHODS: The authors tested the feasibility of combining concurrent infusional leucovorin (500 mg/m2/d) with protracted infusional 5-FU (200 mg/m2/d) and weekly bolus cisplatin (20 mg/m2) in 22 patients with metastatic colorectal cancer. RESULTS: Four partial responses (PR) were noticed among 21 evaluable patients (19%). The median time to treatment failure and median survival were 6 months and 11 months, respectively. All but two patients required 5-FU dose reduction after a median of 2 weeks because of mucositis. However, severe mucositis and diarrhea occurred in only 18% and 5% of the patients, respectively. Palmar-plantar erythrodysesthesia of mild to moderate severity occurred in 55% of patients. Megaloblastic changes were evident in the peripheral blood during therapy, and may reflect prolonged DNA-directed toxicity of 5-FU. The median tolerated dose level of 5-FU was 113 mg/m2/d (range, 64-150 mg/m2/d). Mean steady-state plasma concentrations (Cpss) of 5-FU appeared to increase linearly from 0.19 microM to 0.39 microM over the dose range 64 to 200 mg/m2/d. Patients with grade 2 gastrointestinal toxicity had significantly higher 5-FU Cpss than patients with grade 0 or 1 toxicity. CONCLUSIONS: The early onset of toxicity with this regimen of protracted infusional 5-FU/high-dose leucovorin and weekly cisplatin required marked attenuation of the 5-FU dose intensity, and the results were no better than that expected with infusional 5-FU alone.

Adult↗

Hyperstimulation affects vascular permeability at implantation sites in the rat endometrium.

PURPOSE: It has previously been shown that deleterious changes occur in the epithelium and stroma of the endometrium of the rat following ovarian hyperstimulation by exogenous gonadotropins. The purpose of the present study was to investigate the formation of possible implantation sites following hyperstimulation. Female rats (n = 8) were injected in phase with their estrous cycle with follicle stimulating hormone (FSH), followed by human chorionic gonadotropin (hCG), and mated at proestrous. Control rats (n = 6) were uninjected and mated at proestrous. Animals were killed at 5.5 days of pregnancy. The pontamine blue technique was used to demonstrate the permeability of the uterine vessels. Implantation sites were demonstrated in the uterine horns of all control animals by segmental blue banding. RESULTS: Blue staining occurred only in a portion of one horn of one hyperstimulated animal. While fenestrations were found in the walls of capillaries of control animals, similar fenestrations were not observed in the vessels of hyperstimulated animals. CONCLUSION: As the walls of vessels in the hyperstimulated animals failed to become permeable, and as no implanting embryos were found in these animals, it is concluded that there was an inability of the endometrium to form implantation sites. These changes may impede attachment and implantation of the embryo.

Animals↗

Diet as risk and therapy for cancer.

This article provides a brief overview of the scientific rationale for dietary guidelines that may reduce the risk of some types of cancers--breast, colon, and prostate in particular. Dietary modification clinical trials currently sponsored by the National Cancer Institute are described. Other topics include the role of total parenteral nutrition in cancer therapy and low-fat dietary interventions as an adjunct to breast cancer treatment.

Diet↗

Expanding horizons in breast and prostate cancer prevention and early detection. The 1992 Samuel C. Harvey Lecture.

Breast cancer and prostate cancer, the most common cancers in American women and men, respectively, are major public health concerns. Investigations into the prevention and early detection of breast and prostate cancer include research on the potential impact of diet, particularly dietary fat, on breast cancer risk; the chemoprevention of breast cancer using tamoxifen and N-(4-hydroxyphenyl)retinamide(4-HPR); the importance of mammography in early detection of breast cancer; the potential of finasteride in preventing or retarding the progression of early-stage prostate cancer; and improved detection of prostate cancer by combining various screening modalities. The importance of transferring information gained though such research to the health care community cannot be overemphasized. Further, it is critical that cancer prevention and detection education be built into the curricula of leading medical and biomedical institutions. Education is key to developing a strong and vigorous cancer prevention and early detection research program.

Antineoplastic Agents↗

Dose-dependent effects of exogenous gonadotrophins on the endometrium of the rat.

We compared the serum levels of oestrogen and progesterone and the endometrial morphology of normal pregnant rats at 5,5 days' gestation with those of pregnant rats given either low (10 IU) or high (20 IU) doses of two gonadotrophins: follicle-stimulating hormone (FSH) and human chorionic gonadotrophin (HCG). Evidence of ovarian hyperstimulation was observed in the high- but not the low-dose group; both treatment regimens caused significant changes in the endometrial surface, epithelial height, the microvillous border, the glycocalyx, the subepithelial stromal cells and the mitotic activity of the surface epithelial and stromal connective tissue cells. The effects of the high-dose treatment were more severe than those of the low-dose treatment. The serum oestradiol and progesterone levels of the treated groups were not significantly different from those of the control group. The changes in the endometrium after both treatment regimens may interfere with normal trophoblastic-endometrial interactions and could influence the maintenance of pregnancy. This investigation demonstrated that even low doses of gonadotrophins, which do not cause obvious ovarian stimulation, affect uterine morphology. The findings have important implications for in vitro fertilisation and embryo transfer programmes.

Animals↗

Does the AHA/ACC task force grading system predict outcome in multivessel coronary angioplasty?

To assess the ACC/AHA task force grading system as a predictor of outcome in patients undergoing multivessel percutaneous transluminal coronary angioplasty we analyzed all failures (residual stenosis > 50%, Q-wave myocardial infarction, coronary artery bypass grafting during hospitalization, or death) in 97 patients with 328 stenoses. There were 70 males and 27 females; 60 patients had stable angina, and 37 had unstable angina. The mean number of lesions dilated per patient was 3.4 (range 2-8). The mean preangioplasty percent luminal diameter narrowing was 80 +/- 14%. Thirty-eight stenoses were AHA/ACC classification type A, 192 type B, and 98 type C. One hundred twenty-eight lesions were located in the left anterior descending artery or its distribution, 89 in the left circumflex, 96 in the right coronary artery, and 15 in other vessels. Procedural success (< 50% residual diameter narrowing and no major ischemic complications) was achieved in 266 lesions (81.1%). Major ischemic complications (death, myocardial infarction, or emergency bypass surgery) occurred in 8 patients (8.2%) and in-hospital mortality was 2%. Analysis on a per stenosis basis demonstrated 84% success in type A, 89% in type B, and 64% in type C (p < 0.0001). When type B was divided into type B1 (1 type B characteristic) and type B2 (two or more type B characteristics) the success rate was 90% vs. 88% and the complication rate was 1% vs. 2%, respectively (p = n.s.). Logistic regression analysis showed that the best single predictor of failed angioplasty was total occlusion > 3 months, followed by total occlusion < 3 months and severely angulated (> 90 degrees) segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗