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Biomedical subjects

L A Lambert

Publications and source records attributed to L A Lambert.

At least 19 recordsLinked to original sources
PubMed2003

A network-informed approach to investigating a tuberculosis outbreak: implications for enhancing contact investigations.

BACKGROUND: To elucidate networks of Mycobacterium tuberculosis transmission, it may be appropriate to characterize the types of relationships among tuberculosis (TB) cases and their contacts (with and without latent TB infection) in addition to relying on traditional efforts to distinguish 'close' from 'casual' contacts. SETTING: A TB outbreak in a US low incidence state. OBJECTIVE: To evaluate whether social network analysis can provide insights into transmission settings that might otherwise go unrecognized by routine practices. DESIGN: All adult outbreak-associated cases (n = 19) and a convenience sample of their contacts with and without latent TB infection (LTBI) (n = 26) were re-interviewed in 2001 using a structured questionnaire. Network analysis software was used to create diagrams illustrating important persons within the outbreak network, as well as types of activities TB cases engaged in with their contacts. RESULTS: Drug use and drug sharing were more commonly reported among cases and their infected contacts than among contacts without LTBI. TB cases central to the outbreak network used crack cocaine, uncovering the need to focus control efforts on specific sites and persons involved in illicit drug use. CONCLUSION: Outbreaks occur even in areas with low TB incidence, frequently among groups whose drug use or other illegal activities complicate control efforts. TB programs should consider the use of network analysis as a supplement to routine contact investigations to identify unrecognized patterns of M. tuberculosis transmission.

Adolescent↗
PubMed2001

Intranodal immunization with tumor lysate-pulsed dendritic cells enhances protective antitumor immunity.

We developed a technique for direct inguinal lymph node injection in mice to compare various routes of immunization with tumor lysate-pulsed dendritic cell (DC) vaccines. Syngeneic, bone marrow-derived, tumor lysate-pulsed DCs administered intranodally generated more potent protective antitumor immunity than s.c. or i.v. DC immunizations. Intranodal immunization with ovalbumin peptide-pulsed DCs induced significantly greater antigen-specific T-lymphocyte expansion in the spleen than either s.c. or i.v. immunization. Furthermore, a significantly more potent, antigen-specific TH1-type response to the ovalbumin peptide was induced by intranodal, compared with s.c. or i.v., immunization. Intranodal immunization, designed to enhance DC-T cell interaction in a lymphoid environment, optimizes induction of T lymphocyte-mediated protective antitumor immunity. These results support the use of intranodal immunization as a feasible and effective route of DC vaccine administration.

Animals↗
PubMed2001

Aetiology and treatment of hyperhomocysteinaemia causing ischaemic stroke.

Recent studies have shown that hyperhomocysteinaemia is a common, independent and easily modifiable risk factor for atherosclerotic and thromboembolic diseases such as cerebrovascular disease, coronary artery disease and venous thrombosis. The vascular risk rises continuously across the spectrum of elevated plasma homocysteine concentrations. It is at least as important as cholesterol, lipoprotein abnormalities and hypertension and should be part of risk assessment, especially those at high risk. Moderately elevated plasma homocysteine concentration is readily correctable by folic acid, betaine, or vitamin B12 supplementation. It seems logical to assume that a reduction in homocysteine concentration will reduce the risk of ischaemic stroke, but there are as yet no published data to prove this. This review will discuss the aetiology and possible treatment of hyperhomocysteinaemia causing ischaemic stroke.

Anemia, Pernicious↗
PubMed2000

Impact of HIV-1 infection and highly active antiretroviral therapy on the kinetics of CD4+ and CD8+ T cell turnover in HIV-infected patients.

To evaluate the effects of HIV infection on T cell turnover, we examined levels of DNA synthesis in lymph node and peripheral blood mononuclear cell subsets by using ex vivo labeling with BrdUrd. Compared with healthy controls (n = 67), HIV-infected patients (n = 57) had significant increases in the number and fraction of dividing CD4(+) and CD8(+) T cells. Higher percentages of dividing CD4(+) and CD8(+) T cells were noted in patients with the higher viral burdens. No direct correlation was noted between rates of T cell turnover and CD4(+) T cell counts. Marked reductions in CD4(+) and CD8(+) T cell proliferation were seen in 11/11 patients 1-12 weeks after initiation of highly active antiretroviral therapy (HAART). These reductions persisted for the length of the study (16-72 weeks). Decreases in naive T cell proliferation correlated with increases in the levels of T cell receptor rearrangement excision circles. Division of CD4(+) and CD8(+) T cells increased dramatically in association with rapid increases in HIV-1 viral loads in 9/9 patients 5 weeks after termination of HAART and declined to pre-HAART-termination levels 8 weeks after reinitiation of therapy. These data are consistent with the hypothesis that HIV-1 infection induces a viral burden-related, global activation of the immune system, leading to increases in lymphocyte proliferation.

Antiretroviral Therapy, Highly Active↗
PubMed2000

A nationwide outbreak of alopecia associated with the use of a hair-relaxing formulation.

OBJECTIVE: To study the long-term outcome of adverse effects reported by persons who used a commercial hair-straightening product known as the Rio Hair Naturalizer System (World Rio Corporation). DESIGN: Survey of individuals who contacted the Food and Drug Administration in 1994 and 1995 to report adverse effects linked to using the product. SETTING: Persons residing in the United States. PATIENTS: A total of 464 (59% of 790 eligible) patients who returned a completed questionnaire. MAIN OUTCOME MEASURES: Adverse effects associated with using the Rio Hair Naturalizer System products (neutral or color enhancer). RESULTS: Ninety percent of respondents were African American women between the ages of 15 and 55 years. The most common complaints associated with the use of the products were hair breakage and/or hair loss, reported by 95% of respondents. Three quarters of those experiencing hair loss reported losing 40% or more of their original hair. The median time between the loss of original hair and the growth of new hair was 8 months; however, 40 (9%) respondents reported having no new growth at the time of completing the survey, some 2 years after using the product. When mixed according to package instructions, the mean pH of a sample of 20 neutral product kits tested was 1.39 (range, 1.1-3.15). For the 21 color-enhancer products tested, the mean pH was 2.82 (range, 2. 29-3.08). CONCLUSIONS: A nationwide outbreak of alopecia and scalp injuries involving tens of thousands of women (and some men) occurred following the marketing of a chemical hair-relaxing product. Most of those affected reported substantial hair loss, with a majority indicating growth of new hair that was abnormal in both quantity and quality.

Adolescent↗
PubMed2000

Interval hepatic resection of colorectal metastases improves patient selection.

HYPOTHESIS: Interval reevaluation for resectability of hepatic colorectal metastases aids patient selection. DESIGN: A retrospective review. SETTING: A tertiary care medical center. PATIENTS AND METHODS: From January 1, 1985, to July 1, 1998, 318 patients with colorectal hepatic metastases were identified. Resectable lesions (N = 73) were divided into synchronous (n = 36) or metachronous (n = 37) and retrospectively reviewed for immediate resection or interval reevaluation. Kaplan-Meier survival curves of treatment groups were compared by the log-rank test. RESULTS: Survival curves of patients with synchronous and metachronous lesions undergoing interval reevaluation vs. immediate resection were not significantly different (P = .74 and P = .65, respectively). No lesions from patients who underwent interval reevaluation became unresectable due to growth of the initial metastases. After interval reevaluation, 8 (29%) of 28 patients with synchronous metastases were spared the morbidity of laparotomy because of distant or an increased number of metastases and 10 (36%) of 28 patients were spared the morbidity of hepatic resection at the time of interval laparotomy. Actuarial median and 5-year survival of patients after delayed hepatic resection (51 months and 45%, respectively) were significantly improved compared with those of all other patients with resectable metastases (23 months and 7%, respectively) (P = .02). For patients with metachronous lesions who underwent interval reevaluation, 4 (29%) of 14 patients were spared the morbidity of laparotomy because of an increased number of hepatic or distant metastases. CONCLUSIONS: Delaying hepatic resection for metastatic colorectal cancer does not impair survival. Potentially, two thirds of patients can avoid maj or hepatic surgery. For synchronous metastases, delaying hepatic resection appears to select patients who will benefit from hepatic resection.

Adult↗
PubMed1998

beta-Carotene uptake and effects on intracellular levels of retinol in vitro.

The purpose of the present study was to determine beta-carotene uptake and resultant effects on intracellular levels of retinol in cell lines of varied origin. Human skin fibroblasts, mouse embryonic fibroblasts, rabbit corneal epithelial cells, and rat liver cells were studied. Cells were cultured in medium supplemented with beta-carotene in a water-dispersible beadlet formulation. At selected intervals, cells and media were sampled and analyzed by high-performance liquid chromatography for beta-carotene and retinol content. beta-Carotene was taken up by all four cell lines. An increase in the intracellular levels of retinol was concomitant with beta-carotene uptake in all cell lines. The uptake of beta-carotene and the increase in intracellular retinol were highest in the two fibroblast cell lines. Incubation with media supplemented with crystalline beta-carotene, dissolved in tetrahydrofuran, resulted in significantly lower beta-carotene uptake and intracellular retinol levels. We view these results as a demonstration that a wide variety of cells, cultured in vitro, are able to convert beta-carotene to retinol. Therefore, beta-carotene's provitamin A activity should be carefully considered when the protective effects of beta-carotene in vitro are interpreted.

3T3 Cells↗
PubMed1997

Proteins induced in Escherichia coli by benzoic acid.

Proteins induced by benzoic acid in Escherichia coli were observed on two-dimensional electrophoretic gels (2-D gels). Cultures were grown in glucose-rich medium in the presence or absence of 20 mM benzoate at an external pH of 6.5, where the pH gradient (deltapH) is large and benzoate accumulates, and at an external pH of 8.0, where deltapH is inverted and little benzoate is taken up. Radiolabeled proteins were separated on 2-D gels and were identified on the basis of the index of VanBogelen and Neidhardt. In the absence of benzoic acid, little difference was seen between pH 6.5 and pH 8.0; this confirms that the mechanisms of protein homeostasis in this range are constitutive, including the transition between positive and inverted deltapH. Addition of benzoate at pH 6.5 increased the expression of 33 proteins. Twelve of the benzoate-induced proteins were induced at pH 8.0 as well, and nine of these matched proteins induced by the uncoupler dinitrophenol. Eighteen proteins were induced by benzoate only at pH 6.5, not at pH 8.0, and were not induced by dinitrophenol. One may be the iron and pH regulator Fur, which regulates acid tolerance in Salmonella spp. The other 13 proteins had not been identified previously. The proteins induced by benzoate only at a low pH may reflect responses to internal acidification or to accumulation of benzoate.

Bacterial Proteins↗
PubMed1995

Lack of initiation and promotion potential of deoxynivalenol for skin tumorigenesis in Sencar mice.

The mycotoxin deoxynivalenol (DON; vomitoxin) was tested for its potential to initiate or promote skin tumours through a two-stage treatment regimen in female Sencar mice. DON's capability for initiation was tested by applying a single topical dose (200 micrograms) followed by multiple treatments of the promoter phorbol 12-myristate 13-acetate (PMA). The test for promotion involved initiation with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) followed by multiple DON treatments (50 micrograms). Appropriate control groups were included in the study design. Mice were observed for 26 wk and skin tumours were counted. Results of the study showed that DON was not an initiator or a promoter. When DON was tested as an initiator, there were no statistically significant differences in the number of cumulative tumours or the number of tumour-bearing mice between the DON-initiated/PMA-promoted group and its control, the vehicle-initiated/PMA-promoted group. When DON was administered as a promoter, no tumours were observed. Histopathology of the skin revealed that DON induced a mild diffuse squamous hyperplasia, but there was no progression of the lesion to neoplasia.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

beta-Carotene inhibition of chemically induced toxicity in vivo and in vitro.

In the past several years there has been a great deal of interest in the antioxidant beta-carotene and other micronutrients for their protective potential against various toxic insults. Two studies concerning the protective effects of beta-carotene, which were conducted in our laboratory, are reported here. The first involved the role of beta-carotene in modifying two-stage skin tumorigenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) and promoted by phorbol 12-myristate 13-acetate (PMA, TPA). In this study, the protective effects of two types of dietary beta-carotene, a beadlet formulation and crystalline beta-carotene, were compared in two strains of mice (Skh:HR-1 and CR:ORL Sencar). Mice were maintained on food fortified with 3% beta-carotene or on control diets. Mice receiving the beta-carotene-supplemented diets had fewer tumours than mice in the control groups. However, only in the Skh strain of mice was this difference statistically significant. In the second study, an in vitro experiment, BALBc 3T3 mouse fibroblasts were used to determine beta-carotene's accumulation in cells and the ability of these cells to metabolize beta-carotene to vitamin A. This in vitro model was also used to show a beta-carotene protective effect towards 8-MOP phototoxicity. These studies contributed to the increasing evidence of in vivo and in vitro protection by beta-carotene against chemically induced toxicity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

The protective but nonsynergistic effect of dietary beta-carotene and vitamin E on skin tumorigenesis in Skh mice.

Various epidemiological and experimental studies have indicated that beta-carotene and vitamin E protect against a variety of cancers. This investigation determined whether a synergistic protective effect could be observed against chemically induced skin tumorigenesis in Skh mice by combining these two antioxidants in the diet. Forty-five mice were used in each of four diet groups. Control animals were fed standard mouse chow. Three other groups received the chow supplemented with one of the following: 0.5% beta-carotene, 0.12% vitamin E (added as d-alpha-tocopheryl succinate), or 0.5% beta-carotene + 0.12% vitamin E. Mice were topically treated with a single application of the initiator 7,12-dimethylbenz[a]anthracene and promoted with multiple applications of phorbol 12-myristate 13-acetate. Mice were observed for tumors each week for 27 weeks after initiation. The protective effect of each diet was determined by the decrease in the number of skin tumors in supplemented diet groups compared with that of the control diet group. Decreases in the number of cumulative tumors at Week 27 were 32% for beta-carotene-, 25% for vitamin E-, and 21% for beta-carotene+vitamin E-supplemented diet groups. However, differences in the number of tumors among the three groups supplemented with beta-carotene and/or vitamin E were not statistically significant. Thus, although protection was provided by the individual supplements, there was no synergistic effect for a decrease in the number of chemically induced skin tumors by the simultaneous dietary administration of beta-carotene and vitamin E.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Irreversible conduction block in isolated nerve by high concentrations of local anesthetics.

BACKGROUND: Delivery of large doses of local anesthetics for spinal anesthesia by repeated injections or continuous infusion could expose the cauda equina to concentrations of drug that may be neurotoxic per se. We studied this possible neurotoxic effect by assessing recovery from conduction blockade of desheathed peripheral nerves after exposure to some of the local anesthetic solutions commonly used for spinal anesthesia. METHODS: The reversibility of conduction blockade was studied in desheathed bullfrog sciatic nerves, using the sucrose-gap method for recording compound action potentials, before and during exposure to local anesthetics and during drug washout. The nerves were exposed for 15 min to 5% or 1.5% lidocaine, with or without 7.5% dextrose; 0.5% tetracaine; or 0.75% bupivacaine (the latter two without dextrose). Some nerves were also bathed in 7.5% dextrose (without local anesthetic) or in 0.06% tetracaine, which in this preparation is equipotent to 5% lidocaine. After 15 min in the drug, the nerves were washed for 2-3 h and soaked in Ringer's solution overnight. Nerves exposed only to Ringer's solution served as controls. We also studied neuronal uptake and washout of radiolabeled lidocaine. RESULTS: Exposure of nerves to 5% lidocaine, with or without 7.5% dextrose, or to 0.5% tetracaine resulted in irreversible total conduction blockade, whereas 1.5% lidocaine or 0.75% bupivacaine caused 25-50% residual block after the 2-3 h wash. Nerves exposed to Ringer's solution, 7.5% dextrose or 0.06% tetracaine had 0-10% residual block after 2-3 h wash. The action potential of all nerves declined after overnight soak to between 30-60% of the control value, except for those nerves exposed to 5% lidocaine or 0.5% tetracaine, which showed no activity. Exposure to 5% lidocaine for periods of only 4-5 min produced total, irreversible loss of conduction. The uptake by and washout of radiolabeled lidocaine from the nerves indicate that the maximum amount of residual drug after 2-4 min of exposure to 5% lidocaine and a 3-h wash should cause at most only 50% conduction block. CONCLUSIONS: Solutions of 5% lidocaine and 0.5% tetracaine that have been associated with clinical cases of cauda equina syndrome after continuous spinal anesthesia caused irreversible conduction block in desheathed amphibian nerve. Whether these in vitro actions also occur in mammalian nerves in vivo is an important, clinically relevant question now under investigation in our laboratory.

Analysis of Variance↗
PubMed1993

Criteria for in vitro alternatives for the eye irritation test.

A proposal encompassing considerations and criteria for the development of in vitro alternatives to the eye irritation test has been developed and is presented here. Two factors need to be considered initially in developing an alternative test. The first is to determine whether the alternative assay is to be used as a screen or as a replacement for the eye irritation test. Less stringent acceptance criteria are required for an assay used as a screen than for that used as a replacement test. A screen is a preliminary test for the assessment of eye irritation. It is used for making preliminary decisions or establishing the direction for further testing. Screens answer fewer and less complex questions than a replacement test would, since the results from screens are usually confirmed by more definitive testing. A replacement test, however, must provide the same answers as in vivo methods for the assessment of eye irritation and must provide data for making a definitive toxicological assessment of eye irritation. The second factor to be considered is knowledge of the in vivo assay intended to be replaced. This knowledge should include the procedural aspects of the test and the regulatory information it provides. The following may be considered as criteria for in vitro tests used as screens or as replacements for the eye irritation test in rabbits: rationale (there should be a clear statement regarding the rationale for the use of a particular test in relation to the availability of other tests); relevance (the in vitro endpoint should have biological or physiological relevance to the effect to be detected in vivo); and validational (intralaboratory as well as interlaboratory validation must be conducted).

Animal Testing Alternatives↗
PubMed1993

Screening procedures for eye irritation.

Screens aid in identifying some severe irritants or corrosives and eliminating them from consideration for in vivo eye irritation testing. Products may be evaluated for ocular irritation potential in a stepwise progression as follows: (1) products at pH extremes of 2 or below or of 11.5 or above may be considered to be ocular irritants; (2) based on chemical structure-activity considerations, some products may be judged to have ocular irritation potential; (3) validated and accepted in vitro systems may possibly be used as a screen in the future; (4) when a test material demonstrates severe acute dermal toxicity (lethality at < or = 200 mg/kg body weight), further testing for either dermal or ocular irritation may not need to be undertaken; (5) if a substance shows a primary dermal irritation index of 5 or above, it may be considered to be an ocular irritant; (6) materials that are not removed from consideration based on these proposed screens may then be considered for testing for ocular irritation in rabbits under accepted procedures. In a survey given to participants in the workshop, a high percentage believed that screens should be used. However, opinions on the use of the individual screens varied between the different interested groups attending, with the possible future use of in vitro screens for specific product lines having the highest percentage of agreement (57-100%).

Animal Testing Alternatives↗
PubMed1993

Use of ophthalmic topical anaesthetics.

Pretreatment of the eyes of rabbits with a topical anaesthetic can be viewed as a refinement of the test for eye irritation. It reduces pain at the time of test-material administration, decreases animal distress and permits easier application of the test agent to the eye. In some cases, however, use of an anaesthetic either alone or in combination with the test substance may alter ocular responses or provide little benefit. Although anaesthetic pretreatment may result in decreased pain at the time of test-compound administration, it does not affect possible pain after the effects of the anaesthetic have dissipated. Some anaesthetics are themselves irritating to eyes. In addition, anaesthetics reduce blinking and tearing, thereby maintaining the test-material concentration at the surface of the eye longer. Corneal permeability may also be increased with pretreatment use of an anaesthetic, and may bring the test agent into contact with more structures of the eye. Some anaesthetics delay healing after ocular injury. All of these varied effects may result in increased irritation to the eye. Overall, pretreatment with anaesthetics has usually resulted in a tendency for slightly higher irritation scores; eye irritancy classification is usually unaffected.

Anesthetics, Local↗