PubMed Health⌕ Search

Biomedical subjects

D Lew

Publications and source records attributed to D Lew.

At least 55 records · Page 3Linked to original sources
PubMed1998

Prospective randomized comparison of imipenem-cilastatin and piperacillin-tazobactam in nosocomial pneumonia or peritonitis.

Nosocomial pneumonia and acute peritonitis may be caused by a wide array of pathogens, and combination therapy is often recommended. We have previously shown that imipenem-cilastatin monotherapy was as efficacious as the combination of imipenem-cilastatin plus netilmicin in these two settings. The efficacy of imipenem-cilastatin is now compared to that of piperacillin-tazobactam as monotherapy in patients with nosocomial pneumonia or acute peritonitis. Three hundred seventy one patients with nosocomial pneumonia or peritonitis were randomly assigned to receive either imipenem-cilastatin (0.5 g four times a day) or piperacillin-tazobactam (4.5 g three times a day). Three hundred thirteen were assessable (154 with nosocomial pneumonia and 159 with peritonitis). For nosocomial pneumonia, clinical-failure rates in the piperacillin-tazobactam group (13 of 75 [17%]) and in the imipenem-cilastatin group (23 of 79 [29%]) were similar (P = 0.09), as were the numbers of deaths due to infection (6 in the imipenem-cilastatin group [8%], 7 in the piperacillin-tazobactam group [9%]) (P = 0.78). For acute peritonitis, clinical success rates were comparable (piperacillin-tazobactam, 72 of 76 [95%]; imipenem-cilastatin, 77 of 83 [93%]). For infections due to Pseudomonas aeruginosa, 45 patients had nosocomial pneumonia (21 in the piperacillin-tazobactam group and 24 in the imipenem-cilastatin group) and 10 had peritonitis (5 in each group). In the patients with nosocomial pneumonia, clinical failure was less frequent in the piperacillin-tazobactam group (2 of 21 [10%]) than in the imipenem-cilastatin [corrected] group (12 of 24 [50%]) (P = 0.004). Bacterial resistance to allocated regimen was the main cause of clinical failure (1 in the piperacillin-tazobactam group and 12 in the imipenem-cilastatin group). For the patients with peritonitis, no difference in clinical outcome was observed (five of five cured in each group). The overall frequencies of adverse events related to treatment in the two groups were similar (24 in the piperacillin-tazobactam group, 22 in the imipenem-cilastatin group). Diarrhea was significantly more frequent in the piperacillin-tazobactam group (10 of 24) than in the imipenem-cilastatin group (2 of 22). This study suggests that piperacillin-tazobactam monotherapy is at least as effective and safe as imipenem-cilastatin monotherapy in the treatment of nosocomial pneumonia or peritonitis. In P. aeruginosa pneumonia, piperacillin-tazobactam achieved a better clinical efficacy than imipenem-cilastatin, due to reduced development of microbiological resistance. Tolerance was comparable, with the exception of diarrhea, which was more frequent with piperacillin-tazobactam.

Acute Disease↗
PubMed1998

Heat shock proteins hsp27 and hsp70: lack of correlation with response to tamoxifen and clinical course of disease in estrogen receptor-positive metastatic breast cancer (a Southwest Oncology Group Study).

In this study, we tested the hypothesis that heat shock proteins (hsps) 27 and 70 are associated with clinical resistance to tamoxifen. hsp27 is, like progesterone receptor, an estrogen-regulated protein. hsp70 is also of interest because of its interaction with estrogen receptors and because hsp70 is a component of the molecular chaperone machinery functioning in the assembly and trafficking of steroid receptors. In addition, hsps in general help protect cells against noxious stimuli and stress, and their expression has been linked to drug resistance. The study involved 205 tumors from estrogen receptor-positive tamoxifen-treated breast cancer patients with metastatic disease. All patients received daily tamoxifen as initial therapy for metastatic disease. The study began in 1982, and follow-up is now 9 years. hsp27 and hsp70 were detected by immunohistochemistry and scored according to the nuclear and/or cytoplasmic content. Expression of hsp27 or hsp70 was unrelated to estrogen receptor content, progesterone receptor content, menopausal status, age, and presence of visceral disease. Cytoplasmic and nuclear hsp27 positivities were weakly and inversely related to each other (P = 0.05). There was a significant association between cytoplasmic hsp27 and cytoplasmic hsp70 content (P < 0.001), as well as between nuclear hsp70 and nuclear hsp27 content (P = 0.001). Cytoplasmic and nuclear hsp70 were also associated (P = 0.02). However, increased hsp27 and hsp70 expression (nuclear or cytoplasmic) was not significantly associated with response to tamoxifen, time to treatment failure, or survival. Thus, this study clarifies the lack of clinical utility of hsp27 and hsp70 in predicting the response to tamoxifen in an estrogen receptor-positive breast cancer population.

Adult↗
PubMed1998

Cefepime--assessment of its need at a tertiary care center.

OBJECTIVE: To assess the need and possible indications for a fourth-generation cephalosporin (cefepime). METHOD: A cohort study was carried out over a 17-month period in a 1500-bed Swiss university hospital. RESULTS: In 256 (22.6%) of the 1135 patients followed consecutively by our Infectious Diseases Division, cefepime could have been chosen as an alternative to other broad-spectrum antibiotics, including imipenem/cilastatin (n=94), ciprofloxacine (n=52) and ceftazidime (n=49). Considering the low price-strategy of the pharmaceutical company promoting this drug in Switzerland, there would have been considerable cost savings for the hospital pharmacy if cefepime had been used as first-line treatment in these occasions. Nevertheless, we could not observe any potential advantage of cefepime compared to already introduced broad-spectrum antibiotics, except that cefepime was effective against infections caused by Enterobacter spp. resistant to ceftazidime. CONCLUSION: We conclude that fourth-generation cephalosporins such as cefepime may be introduced into large hospitals only after careful assessment of their potential benefits and that consultation by an Infectious Diseases Division is useful when evaluating the need for new broad-spectrum antibiotics in the hospital setting.

Adult↗
PubMed1997

Repair of craniofacial defects with hydroxyapatite cement.

PURPOSE: The objective of this study was to evaluate the course of healing of craniofacial bone defects when filled with hydroxyapatite cement and to determine whether adding various percentages by weight of demineralized bone powder to the cement will result in enhanced bone formation. MATERIALS AND METHODS: The model for the study was the canine calvarium. The implants were placed into cranial defects and harvested at 3 or 6 months for qualitative evaluation by light microscopy, microradiography, and quantitative histomorphometry. RESULTS: The implantation of hydroxyapatite cement resulted in characteristic replacement of the material with new bone ingrowth. The addition of demineralized bone powder to the hydroxyapatite cement appeared to improve the handling characteristics of the cement; however, improvement in the replacement of the material by bone was not observed. The implantation of only allogeneic demineralized bone showed limited new bone formation within the defect site. CONCLUSIONS: Hydroxyapatite cement formed an effective osseoconductive scaffold for bone replacement. The addition of demineralized bone powder to the cement to serve as a carrier of osseoinductive factors did not result in additional bone being formed.

Animals↗
PubMed1997

Cell response to hyperbaric oxygen treatment.

Wound healing involves matrix deposition, angiogenesis, and new tissue growth. Cellular activity during healing is related to tissue oxygen levels. Since wound healing requires oxygen, the purpose of this study was to investigate the effects of hyperbaric oxygen (HBO) on cells involved in wound healing. Cultured endothelial cells and fibroblasts were exposed to HBO. The effect of varied partial pressure, oxygen saturation, and duration and frequency of exposure to HBO on cell proliferation was determined by 3H-labeled thymidine incorporation. HBO causes an increase in the partial pressure of oxygen in the medium of cultured cells, leading to increased endothelial cell and fibroblast proliferation. Increased endothelial cell proliferation occurred after 15 min of HBO. Fibroblasts required 120 min of HBO to produce a response. A second exposure to HBO on the same day produced no additional increase in cell proliferation. A 120-min HBO exposure stimulated fibroblast proliferation for 72 h after the exposure. An increase in pressure from 2.4 to 4.0 atmospheres absolute did not enhance the proliferative response. These studies begin to elucidate the effects of HBO on cells involved in wound healing and establish a scientific foundation upon which to develop more efficacious and cost-effective HBO therapeutic protocols.

Animals↗
PubMed1996

Effects of antibiotic treatment in the subset of common-cold patients who have bacteria in nasopharyngeal secretions.

BACKGROUND: Upper-respiratory-tract infection is one of the main causes of overuse of antibiotics. We have found previously that bacteria such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae can be isolated from the nasopharyngeal secretions of a substantial proportion of adults with upper-respiratory-tract infections. We have assessed the efficacy of co-amoxiclav in patients with common colds but no clinical signs of sinusitis or other indications for antibiotics. METHODS: Between January, 1992 and March, 1994, 314 patients who presented to our outpatient clinic with common colds were enrolled in the double-blind, placebo-controlled study. They were randomly assigned 5 days' treatment with co-amoxiclav (375 mg three times daily) or identical placebo. Clinical examinations were done at enrolment and on day 5-7 to assess outcome (cured, persistent symptoms, worse symptoms). Seven patients were excluded after randomisation, seven did not have nasopharyngeal aspiration, and 12 did not return for followup assessment. FINDINGS: Of 300 patients with nasopharyngeal aspirates, 72 had negative bacterial cultures, 167 had cultures positive only for bacteria unrelated to respiratory infections, and 61 had cultures positive for H influenzae, M catarrhalis, or S pneumoniae. At 5-day follow-up of these culture-positive patients, the distribution of outcome was significantly better among co-amoxiclav-treated (n=30) than placebo-treated (n=28) patients (cured 27 vs 4%; persistent symptoms 70 vs 60%; worse symptoms 3 vs 36%; p=0.001). Patients on co-amoxiclav also scored their symptoms significantly lower than patients on placebo (p=0.008). Among culture-negative patients (n=230), the outcome distribution did not differ between the treatment groups (p=0.392). INTERPRETATION: The majority of patients with upper-respiratory-tract infection do not benefit from antibiotics and side-effects are frequent. However, for the subgroup whose nasopharyngeal secretions contain H influenzae, M catarrhalis, or S pneumoniae, antibiotics are clinically beneficial.

Adult↗
PubMed1996

Evaluation of topotecan in patients with recurrent for metastatic squamous cell carcinoma of the head and neck. A phase II Southwest Oncology Group study.

Twenty-nine patients with persistent, recurrent and/or metastatic squamous cell carcinoma of the head and neck were treated daily for five days at three-week intervals with topotecan 1.5 mg/m2. Four patients received prior chemotherapy, 23 prior surgery and 29 prior radiation therapy. Of the 29 eligible patients, 8 patients were not evaluable for response and were assumed to be non-responders. Of the remaining 21 evaluable patients, there were zero responses (0%, 95% confidence interval [0,.12]). The most common toxicities were myelosuppression, dyspnea and malaise/fatigue/lethargy. Topotecan has limited activity in advanced head and neck cancer with this dose and schedule.

Adult↗
PubMed1996

A study of the control of disc movement within the temporomandibular joint using the finite element technique.

PURPOSE: A two-dimensional finite element model was developed to simulate and study the in vivo biomechanics and mechanisms of the human temperomandibular joint (TMJ) over the range of normal motion. MATERIALS AND METHODS: A nonlinear model was developed and run using the commercially available ABAQUS software with slide line elements that allowed large displacements and arbitrary contact of surfaces. The three main components of the model were the mandibular condyle, articular disc, and glenoid fossa region of the temporal bone, which were all modeled as deformable bodies. Continuous motion was simulated by doing a static analysis for each of many small steps. A parametric study was performed by determining the maximum stress in each of the three main components as a function of the elasticity of the articular disc. RESULTS: The articular disc was found to move along with condyle in a lifelike manner, even when there were no attachments to the disc. Stress distribution plots showed relatively high stresses deep in the glenoid fossa for most steps. There was a direct, although nonlinear, relationship between maximum stress for all three components and the stiffness of the disc. CONCLUSIONS: This model suggests that muscle contraction is not required to maintain proper disc position. Normal motion results in relatively high stresses deep in the glenoid fossa. The elasticity of the in vivo articular disc may be closer to the lower end of the reported values.

Biomechanical Phenomena↗
PubMed1996

Modified brow lift: an adjunct to blepharoplasty.

PURPOSE: This report evaluates the efficacy of the modified supratrichial brow lift technique. The indications for the procedure, as well as the advantages, effectiveness, and complications are reviewed. PATIENTS AND METHODS: Thirty-six modified supratrichial brow lift procedures were performed bilaterally on 34 female and two male patients. The procedure was used in conjunction with a blepharoplasty in 32 patients and alone in four patients. RESULTS: The procedure improved the cosmetic result in the 32 patients with lateral brow ptosis who had a concomitant upper eyelid blepharoplasty. No complications were encountered. CONCLUSION: The modified supratrichial brow lift can improve the cosmetic result in patients with lateral brow ptosis undergoing an upper eyelid blepharoplasty.

Adult↗
PubMed1996

The molecular epidemiology of tuberculosis in New York City: the importance of nosocomial transmission and laboratory error.

SETTING: During the 1980s, New York City experienced a rapid increase of tuberculosis cases, more than 40% of which were human immunodeficiency virus (HIV)-associated. OBJECTIVE: To better define the molecular epidemiology of tuberculosis in New York City. DESIGN: We collected an isolate from every patient in New York City with a positive culture for Mycobacterium tuberculosis, including both incident and prevalent cases, in April 1991. Restriction fragment length polymorphism (RFLP) analysis using IS6110 was performed and the clinical, demographic, epidemiologic, and drug susceptibility patterns of patients were correlated with RFLP results. RESULTS: Of 441 patients, 12 (3%) had laboratory, clinical, and RFLP evidence of falsely positive cultures. The remaining 429 patients had 252 distinct RFLP patterns. Patients with clustered 1-3 band isolates did not share demographic or drug susceptibility patterns. Eliminating these patients from the analysis, 344 patients remained, of whom 126 (37%) belonged to one of 31 clusters ranging in size from 2-17 patients (median cluster size = 3). Clustering was more common among patients with multidrug-resistant isolates (53%), African Americans (44%), and the homeless (49%), but was not associated with HIV infection or acquired immune deficiency syndrome (AIDS), Multidrug-resistance, being African American, and homelessness remained independently associated with clustering in multivariate analysis. Of 79 patients in clusters of > or = 4 patients, 25 (32%) had identifiable epidemiologic linkages; 17 (74%) of these patients, and 6% of all cases, were documented to have been nosocomially associated. CONCLUSION: A small but non-negligible proportion (3%) of New York City patients had falsely positive cultures for M. tuberculosis as a result of laboratory error. More than one third of all patients and most patients with multidrug-resistance in April 1991 had clustered RFLP patterns, suggesting recent transmission of M. tuberculosis. Homelessness, multidrug-resistance, and being African American independently increased the risk of clustering. Most of the identified epidemiologic linkages and 6% of all cases resulted from transmission in hospitals.

AIDS-Related Opportunistic Infections↗
PubMed1996

DNA immunization against experimental genital herpes simplex virus infection.

A nucleic acid vaccine, expressing the gene encoding herpes simplex virus (HSV) type 2 glycoprotein D (gD2) under control of the cytomegalovirus immediate-early gene promoter, was used to immunize guinea pigs against genital HSV-2 infection. The vaccine elicited humoral immune responses comparable to those seen after HSV-2 infection. Immunized animals exhibited protection from primary genital HSV-2 disease with little or no development of vesicular skin lesions and significantly reduced HSV-2 replication in the genital tract. After recovery from primary infection, immunized guinea pigs experienced significantly fewer recurrences and had significantly less HSV-2 genomic DNA detected in the sacral dorsal root ganglia compared with control animals. Thus, immunization reduced the burden of latent infection resulting from intravaginal HSV-2 challenge, and a nucleic acid vaccine expressing the HSV-2 gD2 antigen protected guinea pigs against genital herpes, limiting primary infection and reducing the magnitude of latent infection and the frequency of recurrent disease.

Animals↗
PubMed1996

Regression analysis with missing covariate data using estimating equations.

In regression analysis, missing covariate data has been among the most common problems. Frequently, practitioners adopt the so-called complete-case analysis, i.e., performing the analysis on only a complete dataset after excluding records with missing covariates. Performing a complete-case analysis is convenient with existing statistical packages, but it may be inefficient since the observed outcomes and covariates on those records with missing covariates are not used. It can even give misleading statistical inference if missing is not completely at random. This paper introduces a joint estimating equation (JEE) for regression analysis in the presence of missing observations on one covariate, which may be thought of as a method in a general framework for the missing covariate data problem proposed by Robins, Rotnitzky, and Zhao (1994, Journal of the American Statistical Association 89, 846-866). A generalization of JEE to more than one such covariate is discussed. The JEE is generally applicable to estimating regression coefficients from a regression model, including linear and logistic regression. Provided that the missing covariate data is either missing completely at random or missing at random (in addition to mild regularity conditions), estimates of regression coefficients from the JEE are consistent and have an asymptotic normal distribution. Simulation results show that the asymptotic distribution of estimated coefficients performs well in finite samples. Also shown through the simulation study is that the validity of JEE estimates depends on the correct specification of the probability function that characterizes the missing mechanism, suggesting a need for further research on how to robustify the estimation from making this nuisance assumption. Finally, the JEE is illustrated with an application from a case-control study of diet and thyroid cancer.

Biometry↗
PubMed1995

An N-terminal deletion mutant of estrogen receptor exhibits increased synergism with upstream activators and enhanced binding to the estrogen response element.

To study the role of the N-terminal region of the estrogen receptor (ER) in transcription activation and in DNA binding, we constructed a mutant of the Xenopus laevis ER which lacks amino acids 1-159 (XER160/586). In transient transfections, XER160/586 exhibited < 10% of the activity of wild-type XER on a synthetic promoter containing two estrogen response elements (EREs). To examine transcriptional synergism by XER and by XER160/586, we determined the activity of promoters containing EREs and binding sites for either the vitellogenin activator, NF1, or AP1 upstream activator protein. For the three promoters transcription by XER was 2.8-fold greater than expected for additive activities, and transcription by XER160/586 was 6.2-fold greater. These data demonstrate that an upstream activator protein bound near the promoter can partially compensate for the loss of the internal N-terminal (AF1) transactivation domain in XER160/586. Using a promoter interference assay to study the intracellular interaction between ER and the estrogen response element, we found that XER160/586 exhibited a significant increase in affinity for the ERE. Its low basal activity and enhanced affinity for the ERE make XER160/586 an effective dominant negative mutant. When co-expressed with wild-type XER at 1:1 and 5:1 ratios, XER160/586 suppressed the activity of wild-type XER by 57% and > 80%, respectively.

Animals↗
PubMed1995

Rhytidectomy: use of the short flap.

PURPOSE: This study compares the use of the short and long flap rhytidectomy. PATIENTS AND METHODS: Thirty short flap rhytidectomies and 20 long flap rhytidectomies were compared for indications, operating time, complications, and patient satisfaction. Flaps 6 cm or less in length were considered short flaps. RESULTS: The short flap technique was used more frequently on younger female patients. The use of this technique resulted in fewer complications and shortened operating and anesthesia times. Patient satisfaction was the same with both procedures. CONCLUSION: The short flap technique is appropriate for the younger patient with minimal nasolabial folds, jowls, rhytids, actinic damage, and less extensive signs of aging. When this technique is used on a suitable patient, the results are cosmetically gratifying.

Adult↗