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Biomedical subjects

L Slater

Publications and source records attributed to L Slater.

At least 19 recordsLinked to original sources
PubMed2001

Enzyme immunoassay for the diagnosis of cat-scratch disease defined by polymerase chain reaction.

Whole-cell immunofluorescent antibody (IFA) tests for detection of anti-Bartonella henselae immunoglobulin (Ig) G are commonly used to diagnose cat-scratch disease (CSD). The need to cultivate B. henselae in Vero cells for antigen preparation and the absence of routinely applied IFA assays for IgM constitute the major disadvantages of this form of test. We describe the results of an enzyme immunoassay (EIA) for IgM and IgG that used N-lauroyl-sarcosine-insoluble outer membrane antigens from agar-grown B. henselae performed in 84 patients with definite CSD (regional lymphadenitis, cat contact, and > or =1 confirmatory test: polymerase chain reaction, skin test, or B. henselae culture). Although this method has been used as a diagnostic tool in several case reports, it has not previously been evaluated in a large study of definitively proven CSD cases. Results of this study indicate that the EIA described herein can play an important role in the serodiagnosis of CSD, although improvement of the sensitivity, particularly that of the IgM, would be desirable.

Adolescent↗
PubMed2001

Evaluating the quality of systematic reviews in the emergency medicine literature.

STUDY OBJECTIVE: The objective of this study was to examine the scientific quality of systematic reviews published in 5 leading emergency medicine journals. METHODS: MEDLINE and EMBASE databases were electronically searched to identify published systematic reviews. Searches were only conducted in emergency medicine journals during the past 10 years; 4 of the journals were also hand searched. Potential reviews were assessed independently by 2 reviewers for inclusion. Data regarding methods were extracted from each review independently by 2 reviewers. All systematic reviews were retrieved and rated for quality by using the 10 questions from the overview quality assessment questionnaire. RESULTS: Twenty-nine reviews were identified from more than 100 citations. The overall scientific quality of the systematic reviews was low (mean score, 2.7; 95% confidence interval 2.1 to 3.2; maximum possible score, 7.0). Selection and publication biases were rarely addressed in this collection of reviews. For example, the search strategies were only identified in 9 (31%) reviews, whereas independent study selection (6 [21%]) and quality assessment of included studies (9 [31%]) were infrequently performed. Overall, the majority of reviews had extensive flaws, and only 3 (10%) had minimal flaws. CONCLUSION: The results of the study indicate that many of the systematic reviews published in the emergency medicine literature contain major flaws; reviews with poor methodology may limit the validity of reported results. Further efforts should be made to improve the design, reporting, and publication of systematic reviews in emergency medicine.

Emergency Medicine↗
PubMed2000

Extracellular Bartonella henselae and artifactual intraerythrocytic pseudoinclusions in experimentally infected cats.

Blood, spleen and liver of specific pathogen-free (SPF) cats and SPF cats experimentally infected with Bartonella henselae were examined. Using immunohistochemical labeling, no intracellular B. henselae were observed in tissues of any cats, but extracellular B. henselae were detected in tissues of infected cats. Pseudoinclusions were detected in erythrocytes of all cats using electron microscopy.

Animals↗
PubMed1999

Immune response of neonatal specific pathogen-free cats to experimental infection with Bartonella henselae.

The purpose of this study was to determine whether neonatal cats develop and maintain a persistent bacteremia for longer than do adult cats with a normal mature immune system, and whether neonatal cats are susceptible to infection with Bartonella henselae by oral inoculation. Neonatal specific pathogen-free (SPF) cats were inoculated with B. henselae intradermally (n = 4) or orally (n = 5) or with 0.9% NaCl (n = 2). Blood was collected periodically through 16 weeks post-inoculation (PI) for serology, bacteriology and complete blood count. Cats inoculated orally or intradermally at 3-5 days of age were bacteremic through 12-16 weeks PI, similar to what is documented for adult cats inoculated intradermally or intravenously. One cat inoculated at age 2 weeks was bacteremic through 10 weeks PI; the other was not bacteremic. Intradermally inoculated neonatal cats produced serum IgG antibodies to B. henselae but orally inoculated neonatal cats did not. Infected cats with and without serum IgG antibodies to B. henselae became blood-culture negative simultaneously, suggesting that IgG is not required to clear bacteremia.

Animals↗
PubMed1999

Evaluating the outcomes of low vision rehabilitation.

The requirement for those providing healthcare to measure outcomes raises the fundamental question of how these should be measured. Both the scale of the low vision population and the different models of care proposed make it a pressing need to determine outcomes using valid and reliable measures. In this study we describe the development and piloting of a questionnaire designed to meet this requirement. The questionnaire was piloted on 56 subjects with age-related macular degeneration (ARMD). Test-retest reliability of the questionnaire was estimated using a further sample of 28 subjects with ARMD. Pilot testing confirmed the feasibility of administering the questionnaire to an elderly population with ARMD. A total of 87% of the sample reported using an LVA (65% on a daily basis), predominantly for a reading task. The number of tasks an LVA was used for, its frequency of use, length of continuous use and ease of use are significantly associated with the rating of an LVA as important/less important (P < 0.0001), but the acuity achieved with the device is not significantly associated with rated importance (P = 0.11), reinforcing doubt about the validity of visual function outcomes. The limitations of this pilot study and earlier case series in describing the outcomes of low vision care are discussed and a randomised controlled trial using a broad range of outcomes is proposed in order to fully describe the effectiveness of low vision rehabilitation and inform the debate about models of care.

Aged↗
PubMed1997

Oral mucosal melanomas: the WESTOP Banff workshop proceedings. Western Society of Teachers of Oral Pathology.

A workshop to discuss primary oral melanomas was convened at the annual Western Society of Teachers of Oral Pathology meeting in Bannf, Alberta, Canada. Fifty oral melanomas, identified from the files of the participants, were reviewed in order to better understand the clinical features, histologic spectrum, and natural history of these perplexing lesions. Results confirmed that oral melanomas occur in adults almost three times more frequently in men than women and have a decided predilection for the palate and gingiva. Some lesions exhibit a clinically detectable and prolonged in situ growth phase, whereas others seem to lack this property and exhibit only or predominantly invasive characteristics. Recurrences, metastases, and death from tumor were characteristic of the follow-up of a limited number of patients. Until definitive prospective data are collected that elucidate natural history, oral mucosal melanomas should be tracked separately from cutaneous lesions. All oral pigmented lesions that are not clinically diagnostic should be biopsied. Lesions with equivocal histopathologic features might be referred to as "atypical melanocytic proliferation" and should be excised. Recognition of lesions in an early in situ phase and aggressive treatment should have a favorable effect on prognosis. To enhance future or prospective study of these rare neoplasms, guidelines for reporting oral melanomas are suggested.

Adult↗
PubMed1997

Experimental infection of young specific pathogen-free cats with Bartonella henselae.

Eighteen 12-week-old specific pathogen-free cats, blood culture- and serum antibody-negative for Bartonella henselae, were randomly allocated to groups and were intravenously inoculated with 10(10) (group 1), 10(8) (group 2), or 10(6) (group 3) B. henselae or with saline (group 4) or were not inoculated (group 5). Cats were humanely killed at 2, 4, 8, 16, and 32 weeks after inoculation. All B. henselae-inoculated cats were bacteremic by 2 weeks after infection. Bacteremia persisted until 32 weeks after infection in 1 cat. Cats in groups 1 and 2 had fever (>39.7 degrees C) and partial anorexia by 2 weeks after infection that lasted 2-7 days. All infected cats had Bartonella-specific IgM and IgG serum antibodies and lymphocyte blastogenic responses. Histopathologic lesions were observed in multiple organs of infected cats through 8 weeks after infection. Cats were readily infected with B. henselae by intravenous inoculation, developed histopathologic lesions that apparently resolved, and developed B and T lymphocyte responses to infection.

Animals↗
PubMed1995

Collateral sensitivity to radiation and cis-platinum in a multidrug-resistant human leukemia cell line.

Although collateral sensitivity to gamma radiation has previously been described in multidrug-resistant tumor cell lines, we describe here a multidrug-resistant human T-cell acute lymphatic leukemia cell line, L100, which displayed increased sensitivity to both gamma radiation and cis-platinum. Cis-platinum cytotoxicity of parental L0 cells and L100 cells was enhanced, whereas radiation sensitivity of L0 and L100 cells was unaltered by glutathione depletion. These results indicate that disparate mechanisms are operative in the collateral sensitivity of L100 cells to gamma radiation and cis-platinum.

Antineoplastic Agents↗
PubMed1995

Comparison of cyclosporin A, verapamil, PSC-833 and cremophor EL as enhancing agents of VP-16 in murine lymphoid leukemias.

Although verapamil, cyclosporin A. cremophor EL and PSC-833 are active as multidrug resistance modulators, there has been limited study of these compounds as possible chemotherapy enhancing agents against drug-sensitive tumors. We compared these agents as modifiers of VP-16 cytotoxicity in vitro and modifiers of VP-16 efficacy in vivo against drug-sensitive P388 and L1210 leukemias. Our study indicates that cyclosporin A enhances VP-16 cytotoxicity to a significantly greater extent than equimolar concentrations of verapamil or PSC-833. Although cremophor EL shows significantly greater activity than verapamil in VP-16 cytotoxicity enhancement in vitro, it is ineffective when added to VP-16 therapy of mice bearing L1210 leukemia.

Animals↗
PubMed1994

Cyclosporin enhancement of cisplatin chemotherapy in patients with refractory gynecologic cancer. A Gynecologic Oncology Group Study.

BACKGROUND: Cyclosporin has been demonstrated to reverse resistance to several antineoplastic agents including cisplatin in vitro. The purpose of this Phase I trial was to study the potential clinical application of cyclosporin modulation of cisplatin and to establish a tolerable dose of cyclosporin when combined with a standard dose of cisplatin of 75 mg/m2. METHODS: A course of therapy consisted of two cyclosporin infusions over 2 hours each, 24 hours apart, with cisplatin given 6 hours after the first dose. Treatment was repeated every 21 days. Cyclosporin was studied in a Phase I fashion at five different levels, from 1-5 mg/kg per dose. Twenty patients with refractory gynecologic cancer received 81 courses of therapy. All patients had received extensive prior chemotherapy containing cisplatin. RESULTS: Grade 4 nephrotoxicity was seen in 4 of 20 patients: 1 treated at 1 mg/kg, 1 at 2 mg/kg, and 2 at 5 mg/kg of cyclosporin. The patient treated at the 1 mg/kg level was a partial clinical responder and tolerated six courses. The patient at the 2 mg/kg level had received 14 prior courses of cisplatin and tolerated only two additional courses before a Grade 4 renal toxicity developed. Grade 4 nephrotoxicity developed in the two patients receiving 5 mg after two courses of chemotherapy. Two of the 20 patients achieved a complete response (CR) and 3 patients achieved a partial response (PR), for a total response rate of 25% (5 of 20). The two women who achieved CR started treatment with symptomatic ascites; one of whom also had multiple pulmonary lesions that were no longer evident after three courses of therapy. CONCLUSIONS: Cyclosporin at a dose of 4 mg/kg per day given for 2 consecutive days in association with 75 mg/m2 of cisplatin can be given with reasonable assurance of safety.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Rochalimaea species stimulate human endothelial cell proliferation and migration in vitro.

Rochalimaea henselae and R. quintana are associated clinically with proliferative neovascular lesions. The effect of Rochalimaea species on human umbilical vein endothelial cell (HUVEC) proliferation and migration was evaluated in vitro. Cocultivation of Rochalimaea organisms with HUVECs resulted in enhanced HUVEC proliferation. Fibroblast proliferation was unaffected by R. henselae. HUVECs were also stimulated to migrate by Rochalimaea. When R. henselae organisms were disrupted and subjected to centrifugation, the ability to enhance HUVEC proliferation and migration was localized to the particulate, noncytosolic fraction. Trypsin treatment of this fraction diminished its stimulatory activity. These data suggest that the neovascular manifestations of infection with Rochalimaea are likely caused by the production of an angiogenic factor by these bacteria.

Bartonella↗
PubMed1992

Solution conformation of endothelin and point mutants by nuclear magnetic resonance spectroscopy.

Two-dimensional NMR techniques were utilized to determine the secondary structural elements of endothelin-1 (ET-1), a potent vasoconstrictor peptide, and two of its point mutants, Met-7 to Ala-7 (ETM7A), and Asp-8 to Ala-8 (ETD8A) in acetic acid-d3/water solution. Sequence specific NMR assignments were determined for all three peptides, as well as chemical shifts and NOE connectivity patterns. The chemical shifts of ET-1 and ETM7A are identical (+/- 0.05 ppm) except for the site of substitution, whereas marked shift changes were detected between ET-1 and ETD8A. These chemical shift differences imply that the Asp-8 to Ala-8 mutation has induced a conformational change relative to the parent conformation. All three molecules show the same basic nuclear Overhauser effect (NOE) pattern, which suggests that the gross conformation of all three molecules is the same. Small changes in sequential NOE intensities and changes in medium-range NOE patterns indicate that there are subtle conformational differences between ET-1 and ETD8A.

Acetates↗
PubMed1991

Systemic treatment of AIDS-related Kaposi's sarcoma: results of a randomized trial.

PURPOSE: Patients with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi's sarcoma generally respond well to cytotoxic chemotherapy. However, due to the associated myelosuppression, these patients are at risk for developing complicating infections that may affect survival. We therefore conducted a multi-center randomized clinical trial comparing single-agent against combination chemotherapy in advanced AIDS-related Kaposi's sarcoma. Low-dose chemotherapy was employed to evaluate its role in combination therapy for this disease and the toxicities associated with the lower intensity. PATIENTS AND METHODS: Sixty-one patients with extensive mucocutaneous Kaposi's sarcoma or visceral involvement were randomized for treatment with low-dose Adriamycin (doxorubicin, 20 mg/m2) alone (31 cases) or in combination with bleomycin and vincristine (ABV) (30 cases). Patients were randomized within strata based on prognostic features associated with shorter survival in prior studies. Both treatment arms were evenly matched at study entry. RESULTS: Complete and partial tumor remissions were significantly higher with ABV (88%) than with Adriamycin alone (48%) (p = 0.004). The median survival was 9 months in both groups. Study entry criteria significantly associated with shorter survival included CD4 lymphocyte counts less than 100/mm3, hemoglobin level less than 10 g/dL, a history of constitutional symptoms, and a prior history of opportunistic infection(s). Toxicities were similar in both arms, and the regimens were well tolerated. Neutropenia (granulocyte count less than 1,000/mm3) occurred in 34% of patients receiving Adriamycin alone and in 52% of patients receiving ABV and was progressive in successive courses of chemotherapy in both treatment arms. The development of AIDS-defined opportunistic infections was relatively infrequent during therapy (14%). CONCLUSIONS: Low-dose ABV is an effective chemotherapy regimen for the treatment of extensive Kaposi's sarcoma. ABV chemotherapy is associated with significantly higher responses than Adriamycin alone and with acceptable toxicity.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Chemotherapeutic drug sensitivity testing of human leukemia cells in vitro using a semiautomated fluorometric assay.

A simple and reproducible semiautomated fluorometric method for drug sensitivity testing of leukemic cells in microculture is described. The assay is based on hydrolysis of nonfluorescent fluorescein diacetate (FDA) to a strongly fluorescent product (fluorescein) by cells with intact plasma membranes after 72 hr of culture and was in the present study applied to acute lymphocytic leukemia (ALL) cell lines and specimens from patients with lymphocytic and myelocytic leukemia. FDA fluorescence was linearly related to viable cell number within a wide range of cell densities (3-4 logs) as well as in the presence of different added proportions of dead cells. The assay reliably detects high and low grade resistance to vincristine (vcr) and daunorubicin, respectively, as well as the subsequent reversal of vcr resistance by cyclosporin A and the calcium channel blocker verapamil. Using ALL cell lines, drug sensitivity was in good correspondence with data obtained by the microculture tetrazolium assay. Furthermore, drug sensitivity data of fresh leukemia cells from patients with leukemia were readily obtained. The results indicate that the presently described method is applicable for simple and reliable chemosensitivity testing of leukemia cell lines as well as tumor specimens from patients with leukemia.

Cell Count↗
PubMed1988

Correction of altered plasma membrane potentials. A possible mechanism of cyclosporin A and verapamil reversal of pleiotropic drug resistance in neoplasia.

We have recently shown that cyclosporin A (CsA) reverses pleiotropic drug resistance in human acute lymphatic leukemia in vitro and daunorubicin resistance in Ehrlich ascites tumor in vivo. In the present study we examined the mechanisms by which CsA might reverse pleiotropic drug resistance relative to changes in cellular plasma membrane potentials and intracellular calcium ([Ca2+]i). Membrane potentials were measured with DIOC5 dye flow-cytometrically and [Ca2+]i levels with Quin 2 dye spectrofluorimetrically. All pleiotropic (PDR) drug-resistant tumor sublines had decreased membrane potentials (membrane depolarized) compared with their corresponding drug-sensitive parental tumors. In comparison, the membrane potentials of a control antimetabolite-resistant acute leukemia cell line were unchanged. The basal levels of [Ca2+]i in the PDR sublines were variable compared with those of parental drug-sensitive cell lines. Incubation of all PDR tumor sublines with CsA or verapamil resulted in the restoration of membrane potentials to that characteristic of the corresponding drug-sensitive parental tumor. Cyclosporin A produced variable changes in the levels of [Ca2+]i. These data suggest that alteration of membrane potentials is one of the mechanisms responsible for pleiotropic drug resistance in malignancy and show that this alteration is corrected by CsA and verapamil.

Animals↗
PubMed1987

Enhancement by cyclosporin A of daunorubicin efficacy in Ehrlich ascites carcinoma and murine hepatoma 129.

Cyclosporin A abrogates pleiotropic drug resistance in certain experimental tumors. Its impact on drug-sensitive tumors has not been investigated. Our studies show that in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 cyclosporin A enhances daunorubicin inhibition of DNA synthesis in vitro and prolongs survival of host mice in vivo. Of particular interest is that cyclosporin A converts ineffective daunorubicin regimens into those which result in prolongation of host mice survival. Other agents known to reverse pleiotropic drug resistance are reported to exert their effects by increasing intracellular drug accumulation. In contrast, our studies of drug transport in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 show that cyclosporin A causes minimal enhancement of [3H]daunorubicin uptake without inhibition of [3H]daunorubicin efflux in both the presence and absence of interrupted active daunorubicin efflux. This suggests that the mechanism of action of daunorubicin enhancement by cyclosporin A in drug-sensitive tumors is not simply the result of increased intracellular daunorubicin accumulation. In vivo dosages of cyclosporin A in the current study are comparable to those which can be used with reasonable safety in humans. We conclude that cyclosporin A may be useful in the potentiation of anthracycline antibiotic therapy directed against drug-sensitive as well as drug-resistant tumors.

Animals↗