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Biomedical subjects

K Abrams

Publications and source records attributed to K Abrams.

51 records · Page 3Linked to original sources

Effect of organic solvents on in vitro human skin water barrier function.

Skin barrier disruption caused by organic solvents to human cadaver dermatomed skin was evaluated using an in vitro model system. Resultant changes in transepidermal water loss (TEWL), as measured with an evaporimeter, were recorded after topical application of either acetone, chloroform:methanol 2:1, hexane, hexane:methanol 2:3, or the control, water, for exposure times of 1, 3, 6, and 12 min. The resultant lipid/solvent mixture was removed and analyzed for its lipid content. The ability of the different solvents to induce changes in the skin's barrier function was assessed by comparing pre- to post-solvent exposure TEWL (delta TEWL). When compared to the controls, water and unexposed skin, chloroform:methanol 2:1 caused the greatest significant increase in TEWL, followed by hexane:methanol 2:3. Acetone and hexane showed no difference in TEWL from the controls. Besides solvent, exposure time was a significant independent variable for predicting delta TEWL, and the interaction of the two (exposure time and solvent type together) was the strongest predictor. Lipid analysis of the extracts revealed that all the solvents removed comparable quantities of the surface lipids (triglycerides, wax esters, squalene, cholesterol esters). Stratum lipids--ceramides, free fatty acids, and cholesterol--extracted by chloroform:methanol 2:1 and hexane:methanol 2:3 were comparable and significantly greater than those extracted by acetone and hexane. These two solvents failed, however, to induce comparable changes in TEWL, as chloroform:methanol 2:1 induced a significantly greater delta TEWL than hexane:methanol 2:3. Additionally, no individual lipid class extracted by either chloroform:methanol 2:1 or hexane:methanol 2:3 proved to be a significant or accurate variable for predicting delta TEWL. This suggests that the mechanism by which topical chloroform:methanol 2:1 and hexane:methanol 2:3 exposure induce a delta TEWL involves more than pure lipid extraction.

Adolescent↗

Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160.

Simian immunodeficiency virus (SIV) is a primate lentivirus related to human immunodeficiency viruses and is an etiologic agent for acquired immunodeficiency syndrome (AIDS)-like diseases in macaques. To date, only inactivated whole virus vaccines have been shown to protect macaques against SIV infection. Protective immunity was elicited by recombinant subunit vaccines. Four Macaca fascicularis were immunized with recombinant vaccinia virus expressing SIVmne gp160 and were boosted with gp160 produced in baculovirus-infected cells. All four animals were protected against an intravenous challenge of the homologous virus at one to nine animal-infectious doses. These results indicate that immunization with viral envelope antigens alone is sufficient to elicit protective immunity against a primate immunodeficiency virus. The combination immunization regimen, similar to one now being evaluated in humans as candidate human immunodeficiency virus (HIV)-1 vaccines, appears to be an effective way to elicit such immune responses.

Animals↗

Ultraviolet B dose-dependent inflammation in humans: a reflectance spectroscopic and laser Doppler flowmetric study using topical pharmacologic antagonists on irradiated skin.

Normal skin responds acutely to ultraviolet (UV) light exposure with complex inflammatory mechanisms. In the present study UVB irradiation ranging from subclinical erythema doses to twice the minimal erythema dose (24 mJ/cm2 to 96 mJ/cm2) was delivered to the skin of 8 volunteers. Pre-irradiated sites were immediately afterwards exposed to a 24-h occlusive patch containing 1 of 4 anti-inflammatory agents or vehicle control. The resultant change in erythema (vascular reaction) was measured objectively using laser Doppler flowmetry (LDF) and reflectance spectroscopy (RS). The 4 anti-inflammatory compounds reduced the UVB-induced vascular reactions in different and dose-dependent ways. Betamethasone-17-valerate and diphenhydramine were most effective at the 24 mJ/cm2 dose site and indomethacin and acetylsalicylic acid were more effective at sites > or = 48 mJ/cm2. Ranking the reduction in oxygenized hemoglobin (OH) content was as follows: betamethasone-17-valerate (OH reduction = 37.4%) > indomethacin (OH reduction = 21.5%) > acetylsalicylic acid (ASA) (OH decrease = 21.0%) > diphenhydramine (OH reduction = 18.4%). Using LDF, the total ranking of the cutaneous blood flow (BF) reduction was: indomethacin (BF reduction = 39.7%) > betamethasone-17-valerate (BF reduction = 32.7%) > acetylsalicylic acid (BF decrease = 17.5%) > diphenhydramine (BF reduction = 12.3%). Diphenhydramine significantly reduced erythema only at the lowest irradiation dose (24 mJ/cm2) and the decrease in OH was associated with an increased amount of deoxygenized hemoglobin (DOH). A similar slight venous dilatation was present at acetylsalicylic acid-exposed sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

A time-correlation study of ultraviolet B-induced erythema measured by reflectance spectroscopy and laser Doppler flowmetry.

Ultraviolet B (UVB)-irradiated skin pigmentation was quantified using 2 objective and noninvasive techniques. Ten healthy volunteers were exposed to increasing UVB doses in the interval from 6 mJ/cm2 to 120 mJ/cm2 and the resultant vascular and pigmentary changes were evaluated using laser Doppler flowmetry (LDF) and reflectance spectroscopy (RS). Measurements were made 0.25 h, 1 h, 4 h, 8 h, 24 h, 72 h and 192 h post-irradiation. Visual scores were determined 24 h post-irradiation. Both RS and LDF revealed an early and rapid erythematous response to UVB irradiation, peaking between 8 h and 24 h, with no single UVB dose showing any significant increase until 4 h post-irradiation. LDF showed a peak increase in blood flow at 8 h post-irradiation for sites with low UVB exposure (less than or equal to 36 mJ/cm2). Doses greater than or equal to 42 mJ/cm2 showed maximal increase at 24 h. After this increase in blood flow, a slow normalization began that was not complete at 192 h post-irradiation at sites exposed to greater than or equal to 60 mJ/cm2. The present RS analysis is able to distinguish between oxygenized (OH) and deoxygenized hemoglobin (DOH). The only significant increase in DOH was found for the averaged 6 mJ/cm2 and 12 mJ/cm2 UVB dose sites 24 h after irradiation. OH peaked 24 h post-irradiation and resolution was still incomplete after 192 h. RS revealed no dose, as did the LDF, below which the vascular response peaked earlier. LDF measures dermal blood flow and RS measures hemoglobin content in the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Characterization of glutathione S-transferase expression in lymphocytes from chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is a disease state which frequently responds to alkylating agent chemotherapy but ultimately becomes refractory through acquired resistance mechanisms. In the present study, we have examined the expression of glutathione S-transferases (GST) in both CLL and normal control lymphocytes, as these enzymes have been implicated in mechanisms of natural and acquired resistance. Lymphocyte GST was purified from samples by high-pressure liquid affinity chromatography, and subunits were identified by two-dimensional gel electrophoresis and immunoblotting by using polyclonal antibodies specific for individual subunits. Analysis of CLL lymphocyte GST activity using the general substrate 1-chloro-2,4-dinitrobenzene showed a statistically significant 2-fold increase in cells from chlorambucil-resistant patients over those from untreated patients and normal individuals. Furthermore, chlorambucil therapy was seen to cause a 1.3- to 1.5-fold elevation of enzyme activity in three previously drug-naive patients. Analysis of GST isozyme subunits indicated that 95% of the CLL patients examined were positive for the pi isozyme, and this appeared quantitatively to be the major isozyme present. The alpha and mu isozymes were also expressed in 63 and 53% of the patients, respectively. Examination of control lymphocytes, as well as separated B- and T-cell subpopulations, yielded similar results. The present study indicates that a high degree of interindividual variation occurs and that the pattern of CLL lymphocyte GST expression differs from that of other tumor tissues. While there were no obvious correlations between the disease state or stage and isozymes expressed, the quantitative increase in GST activity in chlorambucil-resistant CLL patients may be of relevance to the overall resistant phenotype.

Aged↗

Histologic comparisons of interproximal gingival tissues related to the presence or absence of bleeding.

Interproximal gingival tissues were compared histologically relative to the presence or absence of bleeding after stimulation with a wooden interdental cleaner. Fifteen bleeding and 15 nonbleeding interproximal gingival biopsy specimens were obtained from 30 patients and processed for light microscopic evaluation. Morphometric analysis of tissue components revealed that bleeding areas had a significantly greater per cent of inflamed connective tissue. The inflammatory lesion in the bleeding specimens was primarily in the midinterproximal area. From a diagnostic standpoint, this information provides a rationale for the use of bleeding to detect inflammatory lesions in the midinterproximal region.

Adult↗

Early stopping rules--clinical perspectives and ethical considerations.

A clinical trial should only be launched in the presence of equipoise both amongst clinicians responsible for treating the disease and their patients. However, during the period of patient recruitment the chances are that the levels of equipoise will modify. In some cases, where toxicity or inferiority of efficacy are readily demonstrable, the trial needs to be stopped prematurely to prevent harm to patients. In other cases, the degree of equipoise may be increased by the very existence of the trial or from conflicting evidence reported from other studies. By reference to four specific trials it is argued that instead of definitive rules, the decision as to whether recruitment should be continued must be the role of a Data Monitoring Committee which is able to consider and respond to all the available evidence.

Bias↗

Meta-analysis and the synthesis of evidence.

Use of meta-analytical (quantitative overview) techniques is now commonplace in a large range of medical-research contexts, with a rapid rise in its frequency of use being particularly apparent in the last decade. Many methods of meta-analysis have been proposed and used, from crude 'vote-counting' of studies showing significant or nonsignificant results, through methods for combination of effect-size estimates based on fixed- or random-effects models, to general, linear, mixed models and Bayesian methods. The history of meta-analysis and the advantages and disadvantages of various approaches to it are briefly reviewed in this paper, with reference to its application in health-services research and related fields. Broader approaches to the synthesis of evidence in these contexts using conventional multilevel modelling and hierarchical Bayesian models to address the combination of evidence from disparate types of study are then outlined.

Bayes Theorem↗

Arrowroot as a treatment for diarrhoea in irritable bowel syndrome patients: a pilot study.

OBJECTIVES: Arrowroot is an old-fashioned remedy for diarrhoea, but no clinical studies have been done to evaluate its effectiveness. The aim of this pilot study was to assess its efficacy as a treatment for diarrhoea in 11 patients, all of whom had irritable bowel syndrome with diarrhoea as a feature. METHODS: The patients were interviewed and a questionnaire completed on entry into the trial. They then took 10 mL arrowroot powder three times a day for one month and discontinued the treatment for the subsequent month. Questionnaires were completed after one month on treatment and at the end of the trial after one month off treatment. RESULTS: Arrowroot reduced diarrhoea and had a long-term effect on constipation. It also eased abdominal pain. CONCLUSION: Arrowroot is an effective treatment for diarrhoea. Its action could be explained by several theories which relate to an increase in faecal bulk and thus a more efficient bowel action. The number of patients was small, and further studies are needed to substantiate preliminary results.

Adult↗

Evaluation of protective efficacy of recombinant subunit vaccines against simian immunodeficiency virus infection of macaques.

Simian immunodeficiency virus (SIV) was used as a model to study the protective efficacy of an immunization regimen currently being evaluated as candidate vaccines against HIV in human subjects. Four Macaca fascicularis were first immunized with recombinant vaccinia virus expressing the envelope glycoprotein gp160 of SIVmne and then boosted with subunit gp160. Both cell-mediated and humoral immune responses against SIV, including neutralizing antibodies, were elicited. The macaques were shown to be protected from a homologous virus infection as determined by serology, lymphocyte cocultivation, polymerase chain reactions and in vivo transmission analyses. Four unimmunized control animals were readily infected. However, viremia in infected control animals could decrease substantially following the initial phase of infection so that persistent infection might not be readily detectable.

Animals↗

Pesticide-related dermatoses in agricultural workers.

We need to improve education of farm workers and their families to the potential hazards of exposure to the chemicals and other agents that they are in contact with on a daily basis. Simple measures such as showers in the fields and a change of clothes after work might lower the cutaneous reactions to these chemicals significantly. To that end, physicians can better educate themselves to highlight this area more intensely to residents in training, to offer lectures on the subject at dermatology conferences, and to foster better communication between our public health agencies and the pesticide industry itself. Companies are often cooperative when made aware of the benefits of irritant- and allergic-potential testing. Pesticide registration should require from the companies patch-testing before the product comes to market to determine the threshold irritant concentration and irritant potential of the vehicle.

Agricultural Workers' Diseases↗

Protection of vaccinia-primed macaques against SIVmne infection by combination immunization with recombinant vaccinia virus and SIVmne gp160.

Two Macaca fascicularis with preexisting immunity to vaccinia virus were immunized twice with recombinant vaccinia virus expressing SIVmne gp160. Their SIV-specific antibody responses were lower than that of vaccinia-naive animals immunized similarly. Upon repeated boosting with gp160, the SIV-specific antibody titers in vaccinia-primed animals reached similar levels as vaccinia-naive animals and with comparable neutralizing titers. Both animals were protected against repeated intravenous challenge with low-dose SIVmne E11S. These results are significant because SIVmne E11S infection in M. fascicularis is pathogenic and leads to AIDS-like diseases.

Animals↗