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Biomedical subjects

D L Keefe

Publications and source records attributed to D L Keefe.

At least 55 records · Page 3Linked to original sources
PubMed1996

Transvaginal uterine cervical dilation with fluoroscopic guidance: preliminary results in patients with infertility.

PURPOSE: To assess efficacy of uterine cervical dilation performed with fluoroscopic guidance to treat patients with infertility who have cervical stenosis, false channels within the endocervical canal, or both. MATERIALS AND METHODS: Fifteen patients in whom infertility was diagnosed were referred because the uterine lumen could not be accessed. Three of the patients had endometriosis. With fluoroscopic guidance, the cervix was cannulated and the endocervical canal was dilated with an angioplasty balloon or with dilators. Five patients underwent simultaneous fallopian tube recanalization. Five of 15 patients who underwent dilation subsequently underwent in vitro fertilization for embryo transfer (IVF-ET) or intrauterine insemination. RESULTS: Four patients became pregnant. Of those four, one underwent IVF-ET and one underwent intrauterine insemination. Two patients became pregnant spontaneously. In the five patients who underwent IVF-ET or intrauterine insemination and in the remaining eight patients, the cervix could be easily cannulated up to 7 months after dilation. CONCLUSION: Dilation of the uterine cervix may provide options for treatment in selected patients with infertility. The effect of dilation on patients with other sequelae of cervical obstruction such as endometriosis remains uncertain.

Adult↗
PubMed1995

Similarities and differences between anonymous and directed candidates for oocyte donation.

PURPOSE: To compare anonymous and directed candidates for oocyte donation within a single program. METHODS: 75 consecutive candidates for oocyte donation (49 anonymous and 26 directed) were studied using a semistructured interview to collect data on demographics, psychosocial history, motivation, and candidate views on disclosure to a potential child. RESULTS: Donor groups were similar with regard to race, religion and education. Anonymous donors (mean age 27.33 years, SD 4.17) were significantly younger than directed donors (mean age 37.54 years, SD 4.94), (t = -4.83, df = 73, p < 0.001). Marital duration was significantly longer for directed donors (6.92 years, SD 5.64) versus (2.57 years, SD 3.96) for anonymous donors (t = -3.50, df = 38.47, p = .001). Forty-one percent of anonymous and 69% of directed donors had previous pregnancies (X2 = 4.60, p < .05). A greater percentage of anonymous donors (34.7%) felt that the potential child should be informed of his or her origins, compared to 19% of directed donors, but this difference fell short of statistical significance. CONCLUSIONS: There were more similarities than differences among groups of potential donors with the exception of age, marital status, and previous pregnancies. Differing views about disclosure were suggested in both groups with anonymous donors tending to opt for disclosure.

Adult↗
PubMed1995

Mitochondrial deoxyribonucleic acid deletions in oocytes and reproductive aging in women.

OBJECTIVE: To determine whether oocytes from women harbor deletions in mitochondrial DNA (mtDNA) and whether deleted mtDNA is more common in oocytes from older women than oocytes from younger women. DESIGN: A polymerase chain reaction (PCR)-based strategy, which depends on deletions approximating otherwise widely separated primers to demonstrate mtDNA deletions in individual oocytes, was used. SETTING: Yale In Vitro Fertilization Clinic and Laboratory at Yale University School of Medicine. MAIN OUTCOME MEASURES: Primers flanked a region of the mitochondrial genome in which long direct repeated sequence predispose to deletions. The primers identified the 0.5-kb "common" deletion. Deleted mtDNA was represented by a 0.5-kb band when primers separated by 5 kb were used. Control reactions used primers that amplify mtDNA outside the deletion hotspot. Positive controls included brain and/or muscle from aged individuals, and negative controls included fetal tissue and DNA-free blanks. Nested primers confirmed the specificity of the deleted product. RESULTS: Unfertilized oocytes, muscle, and brain tissue contained PCR products consistent with deleted mtDNA. Fetal tissue lacked the mtDNA deletion product. Deleted mtDNA was detected in single oocytes. Oocytes from older women were more likely to contain deleted mtDNA than oocytes from younger women. CONCLUSION: Deleted mtDNA in unfertilized oocytes may serve as a marker of oocyte senescence.

Adult↗
PubMed1994

Evaluation of suspected deep venous thrombosis in oncologic patients.

Impedance plethysmography (IPG) and duplex scanning with color flow Doppler were performed in 100 consecutive high-risk patients with clinically suspected deep venous thrombosis. Risk factors included recent surgery (< three weeks) in 23%, malignant disease in 91%, clotting abnormalities in 32%, and limited activity in 70%. Lower limb findings of either edema, calf tenderness, or both occurred in 92%. There was agreement between the two tests in 76 patients (29 positive and 47 negative). In 12 patients the IPG was positive and the duplex negative. Four of these had extensive pelvic disease, 2 had lung cancer with an obstructive profile, and 2 had heart failure, all of which are known to cause false-positive IPG results. In the other 12 patients the IPG was negative and the duplex positive; however, 3 of these patients had nonocclusive thrombi, 5 had pelvic disease, and 1 had a hemiparesis of the involved lower limb. In 15 patients (11 with positive duplex studies and 4 with negative) a venogram was obtained and confirmed the results. All patients were followed up clinically and none developed complications suggesting inaccurate duplex results. In conclusion, the IPG is of limited utility in this population with a sensitivity of 71%, specificity of 80%, and false-negative rate of 29% when duplex Doppler and clinical outcome are used as the standard. Where available, duplex Doppler should be preferred for evaluation of suspected deep venous thrombosis in patients with extensive medical disease.

Adolescent↗
PubMed1993

Clinical cardiotoxicity of 5-fluorouracil.

5-Fluorouracil is widely known to be toxic to the hematopoietic and gastrointestinal systems. It also has cardiac toxicity, but this is perceived to be rare. During a 16-month period from January 1990 through April 1991, approximately 910 patients were treated with 5-fluorouracil. Five of these developed life-threatening toxicity consistent with coronary artery spasm for an incidence of .55%. The acute events occurred on the third or fourth day of the 5-day infusion and after the fourth intravenous bolus in the patient on bolus therapy. Each of the patients had ST elevation and ventricular arrhythmias, four had acute myocardial infarction, and two had cardiac arrests. In these cases and those previously reported, cardiac toxicity is consistent with drug- or metabolite-mediated increases in coronary vasomotor tone and spasm, leading to the full spectrum of signs and symptoms of myocardial ischemia in susceptible individuals.

Aged↗
PubMed1993

Estramustine and estrone analogs rapidly and reversibly inhibit deoxyribonucleic acid synthesis and alter morphology in cultured human glioblastoma cells.

Estramustine is an estradiol-based agent that has been shown to accumulate in human glioma cells, resulting in a concentration-dependent alteration in cell size and shape within minutes and an inhibition of proliferation over 3 to 6 days. We evaluated human glioblastoma cultures with [3H]thymidine incorporation assays to determine estramustine's early effects on deoxyribonucleic acid synthesis in these tumors. Because estramustine shares a common structural motif with other antimicrotubule drugs, we synthesized four A-ring conjugates of estrone that contained a carbamate moiety but lacked nitrogen mustard. These analogs were examined by [3H]thymidine incorporation and compared with vinblastine. Greater than 70% inhibition of [3H]thymidine incorporation occurred within 1 hour of treatment with estramustine at 10(-5) mol/L, which increased to 80% inhibition at 4 hours. Ethyl carbamate JE208 was nearly as effective as estramustine in inhibiting deoxyribonucleic acid synthesis, and both were more effective than vinblastine. The inhibitory effects of estramustine and estrone analogs were reversible; vinblastine was not reversible. Although estramustine and JE208 induced similar antiproliferative and morphological changes in glioblastoma cells that persisted for at least 4 days, there was a modest recovery of morphology and thymidine incorporation with JE208 after prolonged treatment. The common findings with estramustine and JE208 suggest that these agents may have a similar mechanism of action and form the basis for the investigation of new agents that may rapidly and reversibly inhibit glioblastoma.

Brain Neoplasms↗
PubMed1992

Quantification of hormone pulsatility via an approximate entropy algorithm.

Approximate entropy (ApEn) is a recently developed formula to quantify the amount of regularity in data. We examine the potential applicability of ApEn to clinical endocrinology to quantify pulsatility in hormone secretion data. We evaluate the role of ApEn as a complementary statistic to widely employed pulse-detection algorithms, represented herein by ULTRA, via the analysis of two different classes of models that generate episodic data. We conclude that ApEn is able to discern subtle system changes and to provide insights separate from those given by ULTRA. ApEn evaluates subordinate as well as peak behavior and often provides a direct measure of feedback between subsystems. ApEn generally can distinguish systems given 180 data points and an intra-assay coefficient of variation of 8%. This suggests ApEn as applicable to clinical hormone secretion data within the foreseeable future. Additionally, the models analyzed and extant clinical data are both consistent with episodic, not periodic, normative physiology.

Algorithms↗
PubMed1991

Usefulness of d, I sotalol for suppression of chronic ventricular arrhythmias.

Sotalol is a unique beta-blocking drug, possessing significant class III antiarrhythmic activity. The efficacy and safety of 2 doses of sotalol (320 and 640 mg/day, divided in 2 doses) were compared to placebo in a 6-week randomized, double-blind, multicenter study of 114 patients with chronic ventricular premature complexes (VPCs) at frequencies of greater than or equal to 30/hour. Sotalol significantly reduced VPCs in patients receiving both low (n = 38) and high (n = 39) doses, compared with patients (n = 37) receiving placebo (by 75 and 88%, respectively, vs 10%; p less than 0.001, sotalol vs placebo; p less than 0.05, high vs low dose). The individual efficacy criterion (greater than or equal to 75% VPC reduction) was achieved in 34% of low-dose and 71% of high-dose sotalol versus 6% of placebo-treated patients (p less than 0.003, sotalol vs placebo; p = 0.007, high vs low dose). Repetitive beats were suppressed 25% by placebo (difference not significant), 80% by low-dose (p less than 0.003) and 78% by high-dose sotalol (p less than 0.005). Sotalol decreased heart rate (by 24 to 25%, p less than 0.001) and increased PR (by 4 to 6%, p less than 0.001) and corrected JT intervals (by 12 to 13%, p less than 0.001), but did not change ejection fraction. Proarrhythmia (nonfatal) occurred in 3 sotalol and in 2 placebo patients. Nine discontinued therapy because of adverse effects (1 low dose and 8 high dose, p less than 0.02). In summary, sotalol is an efficacious antiarrhythmic drug for VPC suppression; in lower doses, it is somewhat less effective but better tolerated.

Adult↗
PubMed1991

Astrocytes within the hypothalamic arcuate nucleus contain estrogen-sensitive peroxidase, bind fluorescein-conjugated estradiol, and may mediate synaptic plasticity in the rat.

Estrogen treatment induces synaptic plasticity accompanied by damaged structures and aggregates of peroxidase in astrocytes in the hypothalamic arcuate nucleus of the rat. Synaptic plasticity also occurs within the arcuate nucleus after physiologic surges of estrogen. Although the function of estrogen-induced peroxidase is unclear at present, in other systems peroxidase can generate free radicals by catalyzing the oxidation of some molecules, including estrogen. Because free radicals underlie remodeling in a number of tissues, estrogen-induced free radicals could mediate synaptic remodeling within the arcuate nucleus. Although they contain estrogen-inducible peroxidase, astrocytes do not contain estrogen receptors as measured by conventional techniques, suggesting that estrogen-inducible peroxidase arises from some novel mechanism. Estrogen could induce peroxidase within receptor-deficient astrocytes by binding to receptors in neurons and stimulating the release of some factor that interacts with astrocytes. Alternatively, estrogen could act directly on astrocytes in the absence of estrogen receptors. Although astrocytes in the hypothalamus of the rat do not contain classical nuclear estrogen receptors, they do bind fluorescein-conjugated estradiol in extranuclear sites. The distribution of fluorescein-conjugated estradiol binding within the hypothalamus overlaps that of peroxidase-rich astrocytes, and double labeling reveals many cells with the stellate morphology of astrocytes, containing both peroxidase and fluorescein-conjugated estradiol binding. However, because peroxidase and fluorescein-conjugated estradiol always occupy different compartments of the cell, the fluorescein-conjugated estradiol is not binding to peroxidase.

Animals↗
PubMed1988

Acute cardiogenic pulmonary edema: clinical and noninvasive evaluation.

Left ventricular echocardiograms performed within ninety-six hours of admission were prospectively correlated with the clinical course in 87 consecutive patients admitted with acute pulmonary edema. Patients were stratified into four groups based on their two-dimensional echocardiogram: hyperdynamic, normal, mildly reduced, and severely reduced. Echocardiographic estimates of left ventricular function were compared with their ejection fraction measured by the gated radioisotope technique. The authors found that 48% of the patients were either normal or hyperdynamic (38% and 10% respectively). Patients in these two groups had a greater incidence of left ventricular hypertrophy (wall thickness greater than 13 mm) (66% vs 39%, p less than .05), hypertension on admission (BP greater than 160/100) (66% vs 41%, p = .05), and smaller end-diastolic dimension (p less than .05) than those with decreased left ventricular function. The authors conclude that echocardiography is a good screening test of left ventricular function in patients presenting with pulmonary edema. Patients with normal or increased left ventricular systolic function should be evaluated for correctable or treatable causes of acute pulmonary edema.

Acute Disease↗
PubMed1987

A cholinergic antagonist, mecamylamine, blocks the phase-shifting effects of light on the circadian rhythm of locomotor activity in the golden hamster.

Despite the well known role of the light-dark cycle in the entrainment of circadian rhythms, very little is known about the neurochemical events that mediate the effects of light on the mammalian circadian clock. Recent anatomical and pharmacological data support the hypothesis that acetylcholine may be involved in relaying light-dark information from the retina to, or within, the circadian clock of rodents. If acetylcholine is required for this response, it should be possible to block the phase-shifting effects of a light pulse by blocking cholinergic neurotransmission. To test this possibility, hamsters free-running in constant darkness received an intraventricular injection of the anticholinergic drug, mecamylamine (450 micrograms), 10 min before being exposed to a 5-min pulse of light known to induce sub-maximal phase shifts in the circadian rhythm of wheel-running behavior. Compared to vehicle-injected control animals, mecamylamine treatment blocked or reduced both the phase-advancing and phase-delaying effects of light. These results support the hypothesis that acetylcholine is involved in mediating the phase-shifting effects of light on the mammalian circadian clock.

Animals↗