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Biomedical subjects

R Levine

Publications and source records attributed to R Levine.

At least 55 records · Page 3Linked to original sources
PubMed1997

Efficacy of pegylated-liposomal doxorubicin in the treatment of AIDS-related Kaposi's sarcoma after failure of standard chemotherapy.

PURPOSE: To determine the efficacy and safety of pegylated-liposomal doxorubicin in patients with AIDS and Kaposi's sarcoma (AIDS-KS) who experienced failure of standard chemotherapy. METHODS: Fifty-three patients with advanced AIDS-KS who experienced disease progression or intolerable toxicities while receiving standard doxorubicin/bleomycin/vincristine (ABV) or bleomycin/vincristine (BV) chemotherapy were identified from a cohort of patients who were then treated with pegylated-liposomal doxorubicin. Patients received 20 mg/m2 pegylated-liposomal doxorubicin (Doxil; Sequus Pharmaceuticals, Inc, Menlo Park, CA) every 3 weeks. RESULTS: Nineteen patients (36%) had a partial response (PR) and one patient had a clinical complete response (CCR). The median duration of response and time (from study entry) to treatment failure were 128 and 134 days, respectively. Of 28 patients who experienced disease progression while receiving combination regimens that contained standard doxorubicin, the PR rate was 32%, which suggests that the pegylated-liposomal encapsulation increases the therapeutic effect of doxorubicin. Patients obtained clinical benefits such as flattening of lesions (48%), improved lesion color (56%), relief of pain (45%), and loss of edema (83%). Forty-nine percent of patients had more than one clinical benefit. The most common adverse effect was leukopenia, which occurred in 40% of patients. Only 15% of patients had nausea and/or vomiting, none of which was severe; 9% experienced alopecia, also generally mild. CONCLUSION: Pegylated-liposomal doxorubicin offers a new alternative for treatment of patients who have experienced failure of standard chemotherapy for AIDS-KS.

Acquired Immunodeficiency Syndrome↗
PubMed1997

p53 gene mutations are common in uterine serous carcinoma and occur early in their pathogenesis.

Uterine serous carcinoma (USC) is an uncommon but aggressive type of endometrial cancer associated with rapid progression of disease and a poor prognosis. Both USC and its recently described putative precursor, endometrial intraepithelial carcinoma (EIC), demonstrate strong p53 overexpression by immunohistochemistry, suggesting alteration of the p53 gene in their pathogenesis. In the present study, we evaluated 21 USCs and 9 EICs for mutations in the p53 gene using direct sequence analysis and found that 90% of USCs and 78% of EICs contain mutations. Significantly, mutations were found in 3 cases of EIC without associated invasive carcinoma and identical mutations were detected in cases with synchronous USC and EIC. Strong p53 immunoreactivity was seen in the majority of USCs and EICs and correlated with p53 gene mutation, although lack of reactivity did not always indicate the absence of a gene mutation. Loss of heterozygosity of chromosome 17p was observed in 100% of USCs and in 43% of EICs, demonstrating that loss of the wild-type p53 allele occurs early in the development of serous carcinoma. Overall, our results reveal that p53 mutations are very common in USC and EIC. The presence of p53 gene mutations in EIC further suggests that p53 alteration plays an important role early in the pathogenesis of serous carcinoma, possibly accounting for its aggressive biological behavior.

Aged↗
PubMed1996

Three-year follow-up of participants in a commercial weight loss program. Can you keep it off?

BACKGROUND: One third of Americans are obese, according to the 1988-1991 National Health and Nutrition Endpoint Survey III survey. Obesity increases the risk of death and a variety of chronic diseases. Numerous commercial weight loss programs demonstrate short-term success. OBJECTIVE: To assess maintenance of weight loss achieved during dieting. METHODS: We surveyed 192 participants in the Sandoz Nutrition (Sandoz Pharmaceuticals, Minneapolis, Minn) diet program approximately 3 years after participation. Initial date were supplied by the diet clinics and follow-up data, including weight at various points after the program, participation in other weight loss programs, and lifestyle variables, such as exercise, smoking, and television watching, were collected by a mailed questionnaire. RESULTS: On average, the group lost 22 kg during the diet program. After the follow-up period, the mean weight (mean, 102.6 kg) was only modestly less than the group's original weight at the start of the diet (mean, 105.9 kg). Twelve percent of the subjects maintained 75% of their weight loss after leaving the diet program, 57% maintained at least 5% of the loss, and 40% gained back more than they had lost during the diet. The frequency of exercise after the diet program was the strongest predictor of weight loss maintenance, while television viewing predicted a gain in weight. CONCLUSION: Given the apparent lack of substantial, long-term success at weight reduction, perhaps greater emphasis should be placed on prevention of obesity.

Commerce↗
PubMed1996

The bryostatins inhibit growth of B16/F10 melanoma cells in vitro through a protein kinase C-independent mechanism: dissociation of activities using 26-epi-bryostatin 1.

Bryostatin 1 is a potential cancer chemotherapeutic agent in Phase II clinical trials, with positive responses observed for malignant melanoma, among other tumors. The bryostatins are known to be potent ligands for protein kinase C (PKC), functioning as partial antagonists. In the present study, we explore the mechanism by which the bryostatins inhibit growth to B16/F10 mouse melanoma cells in vitro. Three experimental approaches suggest that the growth inhibition is independent of PKC. First, we characterized in detail the translocation and down-regulation of the PKC isozymes alpha, delta, and epsilon in response to phorbol ester and bryostatin 1 in these cells. Although the dose-response curves obtained for the translocation-activation of PKC isozymes showed good correlation with the growth-enhancing activity of phorbol 12-myristate 13-acetate, for no PKC isozyme was there a good correlation with the growth-inhibitory activity of bryostatin 1. Second, inhibition PKC, inhibited the growth of the B16/F10 melanoma cell lines with potency similar to that of bryostatin 1. We confirmed here that 26-epi-bryostatin 1 showed 60-fold reduced affinity for PKC and 30-60-fold reduced potency to translocate and downregulate PKC isozymes compared with bryostatin 1. We presumed that the principal toxicity of bryostatin 1 reflects its interaction with PKC, and we would thus predict that epi-bryostatin 1 would be less toxic. Indeed, we found at least 10-fold reduced toxicity of 26-epi-bryostatin 1 in C57BL/6 mice compared with bryostatin 1. We conclude that the growth inhibition of the bryostatins, at least in this system, does not result from interaction with PKC. As exemplified by 26-epi-bryostatin 1, this insight permits the design of analogues with comparable growth inhibition to bryostatin 1 but with reduced toxicity.

Animals↗
PubMed1996

Initial experience with an implantable hemodynamic monitor.

BACKGROUND: Measurement of intracardiac hemodynamic parameters has been limited to brief periods in the acute care setting. We developed and evaluated an implantable hemodynamic monitor that is capable of measuring chronic right ventricular oxygen saturation and pulmonary artery pressure. METHODS AND RESULTS: The device consists of an electronic controller placed subcutaneously and two transvenous leads placed in the right ventricle (reflectance oximeter) and pulmonary artery (variable capacitance pressure sensor). Implantation was performed in 10 patients with severe left ventricular dysfunction. Average implant pulmonary artery pressures were systolic, 52 +/- 16 mm Hg; diastolic, 29 +/- 11 mm Hg; and mean, 40 +/- 12 mm Hg. The mean right ventricular oxygen saturation at implant was 51%. Provocative maneuvers, including postural changes, sublingual nitroglycerin, and bicycle exercise, demonstrated expected changes in measured oxygen saturation and pulmonary artery pressures over time. At follow-up of 0.5 to 15.5 months, there were no significant differences between pulmonary artery pressures or oxygen saturation values transmitted from the device and simultaneous measurement with balloon flotation catheters. Four of the pulmonary artery leads dislodged and three demonstrated sensor drift, whereas two of the oxygen saturation sensors failed. Four patients died and four received transplants. Pathological study did not demonstrate injury to the right ventricular outflow tract or pulmonic valve. CONCLUSIONS: Chronic measurement of hemodynamic parameters in the outpatient setting with implantable sensor technology appears to be feasible. The devices are well tolerated without significant untoward effects, and the sensors generally function well over time, providing reliable information. Clinical usefulness remains to be established.

Adult↗
PubMed1996

Future directions for resuscitation research. III. External cardiopulmonary resuscitation advanced life support.

This discussion about advanced cardiac life support (ACLS) reflects disappointment with the over 50% of out-of-hospital cardiopulmonary resuscitation (CPR) attempts that fail to achieve restoration of spontaneous circulation (ROSC). Hospital discharge rates are equally poor for in-hospital CPR attempts outside special care units. Early bystander CPR and early defibrillation (manual, semi-automatic or automatic) are the most effective methods for achieving ROSC from ventricular fibrillation (VF). Automated external defibrillation (AED), which is effective in the hands of first responders in the out-of-hospital setting, should also be used and evaluated in hospitals, inside and outside of special care units. The first countershock is most important. Biphasic waveforms seem to have advantages over monophasic ones. Tracheal intubation has obvious efficacy when the airway is threatened. Scientific documentation of specific types, doses, and timing of drug treatments (epinephrine, bicarbonate, lidocaine, bretylium) are weak. Clinical trials have failed so far to document anything statistically but a breakthrough effect. Interactions between catecholamines and buffers need further exploration. A major cause of unsuccessful attempts at ROSC is the underlying disease, which present ACLS guidelines do not consider adequately. Early thrombolysis and early coronary revascularization procedures should also be considered for selected victims of sudden cardiac death. Emergency cardiopulmonary bypass (CPB) could be a breakthrough measure, but cannot be initiated rapidly enough in the field due to technical limitations. Open-chest CPR by ambulance physicians deserves further trials. In searches for causes of VF, neurocardiology gives clues for new directions. Fibrillation and defibrillation thresholds are influenced by the peripheral sympathetic and parasympathetic nervous systems and impulses from the frontal cerebral cortex. CPR for cardiac arrest of the mother in advanced pregnancy requires modifications and outcome data. Until more recognizable critical factors for ROSC are identified, titrated sequencing of ACLS measures, based on physiologic rationale and sound judgement, rather than rigid standards, gives the best chance for achieving survival with good cerebral function.

Animals↗
PubMed1996

Effect of electrosurgical technique on wound healing and early complication rate following abdominal dermolipectomy.

Thirty-eight patients with significant weight loss after vertical banded gastroplasty were studied prospectively while undergoing abdominal dermolipectomy to determine if the current intensity used during electrosurgical dissection influenced wound complication rates after this surgery. Patients were assigned randomly to one of two groups: (1) a HI group, in which the electrosurgical current intensity was set at a level that easily allowed coagulation of all vessels smaller than 0.5 mm in diameter or (2) a LO group, in which the current intensity was set at a much lower level that allowed dissection, but required that nearly all visible vessels be ligated separately. A standardized procedure was employed for all patients. The patients in the LO (N = 14) and HI (N = 24) groups were well matched for age, weight history, nutritional parameters, operative times, surgical blood loss, and postoperative hospital stay. The overall complication rates of 36% and 21%, and wound complication rates of 36% and 13% for the LO and HI groups, respectively, were not significantly different. These data indicate that using a relatively high electrosurgical current intensity for dissection during abdominal lipectomy does not result in a higher wound complication rate.

Abdomen↗
PubMed1996

Differential protein profiles reflect the different lifestyles of symbiotic and aposymbiotic Anthopleura elegantissima, a sea anemone from temperate waters

Mutualistic associations are prevalent in virtually all environments yet relatively little is known about their complex biochemical and molecular integration and regulation. The endosymbiosis between cnidarians such as the sea anemone Anthopleura elegantissima and the photosynthetic dinoflagellate Symbiodinium californium, in which the algal symbionts are housed in vacuoles within animal endodermal cells, is an ideal model for the study of highly integrated associations at the biochemical and molecular levels. This study describes differential protein synthesis between symbiotic A. elegantissima, collected from environments with high levels of light in the intertidal zone and A. elegantissima that naturally lack symbionts (aposymbiotic), collected from nearby deep-shade habitats. Two-dimensional gel electrophoresis profiles of both steady-state and newly synthesized proteins were compared between the two types of animals using scanning densitometry and image analysis. Symbiotic and aposymbiotic animals share a majority of proteins; however, striking differences in several abundant proteins in steady-state profiles occur. Two proteins are unique to symbiotic animals, one at 32 kDa with an isoelectric point (pI) of 7.9 and another at 31 kDa, pI 6.3. Levels of six proteins with an apparent molecular mass of 25 kDa and pI values ranging from 4.8 to 5.5 are greatly enhanced in aposymbiotic animals. Furthermore, profiles of newly synthesized proteins from symbiotic animals contain a unique cluster of proteins ranging from 25 to 30 kDa and pI 6.6 to 6.9. These marked differences in protein profiles must be a reflection either of underlying differences in the regulation of gene expression or in post-translational modification of common proteins. Identifying the symbiosis-specific products present in A. elegantissima and identifying the inter-partner signaling and cues that result in differential expression will provide an insight into the understanding of these highly integrated associations.

Journal Article↗
PubMed1996

PID or Not PID? That Is the Question.

A 14-year-old female was seen for acute abdominal, back, and flank pain, accompanied with dysuria, increased frequency of urination, nausea, and decreased appetite. After an initial diagnosis of pyelonephritis, a presumptive diagnosis of pelvic inflammatory disease (PID) was made. The cervical culture was positive for Chlamydia trachomatis and a pelvic sonogram demonstrated abnormal right adnexal structures and a possible mass. Exploratory laparotomy was performed, which demonstrated right-sided inflammation in the fimbria and fallopian tube as well as an ovarian cyst on the right. Her postoperative course was uncomplicated and was continued on oral doxycycline.

Journal Article↗
PubMed1996

Corona mortis. Incidence and location.

Fifty cadaver halves were dissected to determine the occurrence and location of the corona mortis. Anastomoses between the obturator and external iliac systems occurred in 84% of the specimens. Thirty-four percent had an arterial connection, 70% had a venous connection, and 20% had both. The distance from the symphysis to the anastomotic vessels averaged 6.2 cm (range, 3-9 cm).

Arteries↗
PubMed1995

Comparison of clinically significant infection rates among prehospital-versus in-hospital-initiated i.v. lines.

STUDY OBJECTIVE: To compare the risk of infection for i.v. lines placed in the prehospital versus in the in-hospital setting in a midsized emergency medical service system. DESIGN: A retrospective analysis was made of all i.v. line site infections among patients admitted to ward beds from a university hospital emergency department in 1992. METHODS: The hospital's infection control team conducted daily ward rounds and a surveillance of all wound and blood cultures. Patients with signs and/or symptoms consistent with Centers for Disease Control and Prevention guidelines for skin and soft tissue infection were reported to the responsible medical team. Infections were documented based on consensus opinion between the infection control team and the physicians responsible for the care of the patient. IV lines placed in the prehospital phase of care were identified by electronic retrieval from the prehospital database. RESULTS: Three thousand one hundred eighty-five patients who had a prehospital or an in-hospital i.v. line placed were admitted from the ED. Eight hundred fifty-nine i.v. lines were prehospital placed (27%), and 2,326 were in-hospital placed (73%). There was one infection in the prehospital group and four in the in-hospital group (infection rate: .0012 for prehospital patients and .0017 for in-hospital patients; P = .591 by Fisher's exact test). CONCLUSION: Both cohorts had exceptionally low infection rates. No clinically or statistically significant increase in the risk of infection among prehospital- or in-hospital-initiated i.v. lines was identified.

Arizona↗
PubMed1995

Age effects on lingual pressure generation as a risk factor for dysphagia.

BACKGROUND: Tongue activity plays a crucial role in both oral and pharyngeal phases of swallowing. In this study, maximum lingual isometric and swallowing pressures were quantified in two groups of healthy men to investigate possible age effects on performance. Magnetic resonance images of the brain were also obtained to examine the relationship between age-related anatomical changes and swallowing function. METHODS: Pressures were recorded at three lingual sites (tip, blade, and dorsum) during a maximal isometric task and during saliva swallows. Task order was randomized, and subjects performed three trails per placement site. Additionally, t2-weighted MRIs were obtained on 9 of the 10 young subjects (mean age = 25 years) and all 15 older subjects (mean age = 75 years). RESULTS: Maximal isometric pressures were significantly greater for younger subjects at the tongue blade site (p = .002), whereas peak swallowing pressures remained similar across both age groups. Within-subject comparisons of maximum isometric to swallowing pressures, a measure of reserve capacity, revealed reduced difference scores at the tongue blade in the older group (p = .02). Older subjects exhibited significantly more cerebral atrophy (p = .001) and greater incidence of periventricular white matter lesions (p = .0001) than did younger subjects. CONCLUSIONS: While swallowing pressures remain similar across the life span, overall pressure reserve declines with age. The implications are: (a) older people may be working harder to produce adequate swallowing pressures, and (b) age-related illness may put geriatric patients at higher risk for dysphagia, thus further complicating recovery.

Adult↗
PubMed1995

Bivalvular endocarditis complicating pregnancy. A case report and literature review.

A twenty-nine-year old woman with a history of rheumatic fever and both mitral and tricuspid valve prolapse (without cardiac effects on the echocardiogram) presented with Streptococcus viridans infective endocarditis of both the tricuspid and mitral valves at seventeen weeks' gestation. Twelve weeks before admission she underwent a dental curettage and received presumably adequate antibiotic prophylaxis. The present case was successfully managed by means of aggressive antibiotic therapy appropriate for endocarditis, with adequate and appropriate monitoring of minimal inhibitory concentration and peak and trough levels. This case exhibits the appropriate management in the three phases of therapy for valvular disease, ie prevention, treatment, and subsequent prevention of sequelae, prior to vaginal delivery in a patient with endocarditis. The pregnancy resulted in a term vaginal delivery, without maternal or fetal morbidity.

Adult↗
PubMed1995

MR angiography flow analysis. Neurovascular applications.

The ability to directly measure velocity and volume flow rates adds a new dimension to the MR angiographic evaluation of patients with cerebrovascular disease. Reduced volume flow rates are associated with flow restrictive stenoses. Flow volumes begin to drop when the area of the vessel lumen is reduced by greater than 80%. Cerebrovascular flow reserve also can be determined by obtaining volume flow measurements before and after the administration of a vasodilator such as acetazolamide. Recent applications include the investigation of the flow dynamics associated with subclavian steal, aneurysms, and arteriovenous malformations.

Blood Flow Velocity↗
PubMed1993

Reconstitution of intestinal Na(+)-phosphate cotransporter.

The rabbit intestinal brush-border membrane Na(+)-phosphate cotransporter was purified from sodium dodecyl sulfate (SDS)-brush-border membrane vesicles (BBMV) protein (SDS-treated Ca(2+)-precipitated BBMV) by a three-column chromatography protocol. The purification included a preparative scale chromatofocusing chromatography column over the pH range from 7.4 to 4 after solubilization in 3-[(3-cholamidopropyl)-diamethylammonia]-1-propanesulfonate (CHAPS), a chromatofocusing column over the pH range from 5.6 to 4 after solubilization in n-octyl glucoside, and gel filtration chromatography on a Sephacryl S-200 column. Verification of Na(+)-phosphate cotransporter purification involved substrate affinities, substrate stoichiometry, and inhibitor sensitivity after proteoliposome reconstitution and SDS-polyacrylamide gel electrophoresis (PAGE). After gel filtration Na(+)-dependent phosphate uptake was 3,300-fold enriched compared with the cell homogenate. A single 130-kDa polypeptide was visualized by SDS-PAGE under reducing conditions using silver stain. The coenrichment of this 130-kDa polypeptide and proteoliposome reconstituted Na(+)-dependent phosphate uptake suggest that the intestinal brush-border membrane Na(+)-phosphate cotransporter has been purified and proteoliposome reconstituted.

Animals↗