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Biomedical subjects

D Lew

Publications and source records attributed to D Lew.

At least 19 recordsLinked to original sources
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↗
PubMed1995

Cancer gene therapy using plasmid DNA: pharmacokinetic study of DNA following injection in mice.

The fate of plasmid DNA complexed with cationic lipids delivered intravenously in mice was evaluated at selected timepoints up to 6 months postinjection. Blood half-life and tissue distribution of plasmid DNA and potential expression in tissues were examined. Southern blot analyses of blood indicated that intact plasmid DNA was rapidly degraded, with a half-life of less than 5 min for intact plasmid, and was no longer detectable at 1 hr postinjection. Southern analyses of tissue demonstrated that intact DNA was differentially retained in the lung, spleen, liver, heart, kidney, marrow, and muscle up to 24 hr postinjection. After 7 days, no intact plasmid DNA was detectable by Southern blot analysis; however, the plasmid was detectable by the polymerase chain reaction (PCR) in all tissues examined at 7 and 28 days postinjection. At 6 months postinjection, femtogram levels of plasmid were detected only in muscle. Immunohistochemical analyses did not detect encoded protein in the tissues harboring residual plasmid at 1 or 7 days postinjection.

Animals↗
PubMed1995

Cancer gene therapy using plasmid DNA: safety evaluation in rodents and non-human primates.

To evaluate the safety of a plasmid DNA-lipid complex, a series of good laboratory practice (GLP) safety studies were conducted with VCL-1005, a plasmid DNA expression vector containing both the human class I MHC HLA-B7 heavy-chain and the beta 2-microglobulin (beta 2m) light-chain genes formulated with the cationic lipid, DMRIE/DOPE. In mice, the repeated intravenous injection of VCL-1005 at plasmid DNA doses of 0.1, 1.0, or 10 micrograms for 14 days had only incidental effects on clinical chemistry and hematology, and did not result in any organ pathology. Repeated intrahepatic injections of VCL-1005 in mice did not result in significant liver histopathology or significant alterations in liver enzymes. In cynomolgus monkeys, the repeated intravenous administration of VCL-1005 at a cumulative dose of 720 micrograms of DNA had no effects on clinical chemistry, hematology, or organ pathology. Thus, systemic administration of a plasmid DNA expression vector containing the coding sequence for a foreign MHC class I molecule did not result in significant toxicity or a pathological immune response in animals. These results suggest that the direct transfer of VCL-1005, a plasmid DNA-lipid complex, could be used for the safe in vivo delivery of recombinant DNA for a cancer gene therapy trial.

Animals↗
PubMed1994

Intradermal gene immunization: the possible role of DNA uptake in the induction of cellular immunity to viruses.

The skin and mucous membranes are the anatomical sites were most viruses are first encountered by the immune system. Previous experiments have suggested that striated muscle cells are unique among mammalian cell types in their capacity to take up and express free DNA in the absence of a viral vector or physical carrier. However, we have found that mice injected into the superficial skin with free (naked) plasmid DNA encoding the influenza nucleoprotein gene had discrete foci of epidermal and dermal cells, including cells with dendritic morphology, that contained immunoreactive nucleoprotein antigen. A single intradermal administration of 0.3-15 micrograms of free plasmid DNA induced anti-nucleoprotein-specific antibody and cytotoxic T lymphocytes that persisted for at least 68-70 weeks after vaccination. Intradermal gene administration induced higher antibody titers than did direct gene injection into skeletal muscle and did not cause local inflammation or necrosis. Compared with control animals, the gene-injected mice were resistant to challenge with a heterologous strain of influenza virus. These results indicate that the cells of the skin can take up and express free foreign DNA and induce cellular and humoral immune responses against the encoded protein. We suggest that DNA uptake by the skin-associated lymphoid tissues may play a role in the induction of cytotoxic T cells against viruses and other intracellular pathogens.

Amino Acid Sequence↗
PubMed1994

Aqueous humor penetration of ofloxacin given by various routes.

We studied the aqueous humor penetration of ofloxacin after topical, oral, and intravenous administration in 51 consecutive patients undergoing cataract surgery. Aqueous humor concentration (mean +/- SD) was 0.53 +/- 0.35 mg/l when ofloxacin 0.3% eyedrops were instilled topically six times, one drop every three hours, until 90 minutes preoperatively, and 0.63 +/- 0.29 mg/l (P = .45) when two additional instillations were made, one drop every 30 minutes, until 30 minutes before aqueous humor aspiration. Aqueous humor concentration two hours after a single 200-mg oral dose (0.38 +/- 0.15 mg/l) was significantly lower (P = .048) than that 12 hours after the same oral dose (0.58 +/- 0.24 mg/l). Two hours following an intravenous infusion of 200 mg of ofloxacin, aqueous humor concentration was 0.33 +/- 0.19 mg/l. Our results suggest that therapeutic levels above the minimum inhibitory concentration for many bacteria cultured in endophthalmitis can be achieved in aqueous humor after either topical or oral administration, which indicates that this antibiotic passes easily through the corneal and the blood aqueous barriers.

Administration, Oral↗
PubMed1994

Case report 860: Bacillary angiomatosis of the calcaneum.

Bacillary angiomatosis (BA) is newly reported infectious disease observed mainly in HIV-infected patients, caused by a small gram-negative bacillus of the Rochalimea genus. From a purely dermatological presentation similar to that of Kaposi's sarcoma, it may evolve into a systemic disease. Bone lesions seem fairly frequent. We report a case of an isolated osteolytic lesion due to the BA bacillus.

AIDS-Related Opportunistic Infections↗
PubMed1994

A comparative study of osseointegration of titanium implants in corticocancellous block and corticocancellous chip grafts in canine ilium.

PURPOSE: This study was undertaken to compare the relative rates and extent of osseointegration of dental implants when placed simultaneously with either corticocancellous block or particulate corticocancellous bone grafts. MATERIALS AND METHODS: Using the canine ilium as a model site, the implants were placed so that each served as its own control. The implants were harvested at 1, 2, or 3 months for evaluation by light microscopy, microradiography, and histomorphometry. RESULTS: Both types of grafts were determined to be viable by microscopic evaluation of fluorescent labels. Qualitatively there appeared to be greater bone density in the corticocancellous block graft implant sites. At 3 months, the block graft implant sites had a level of osseointegration (59.6%) that approximated the control implant sites (65.2%), but was significantly greater than the particulate graft sites (39.2%). CONCLUSIONS: These results indicate that implants in corticocancellous block grafts develop osseointegration more rapidly than those in particulate bone grafts. The clinical implications of these findings are discussed.

Animals↗