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Antibacterial and sebosuppressive efficacy of a combination of chloramphenicol and pale sulfonated shale oil. Multicentre, randomized, vehicle-controlled, double-blind study on 91 acne patients with acne papulopustulosa (Plewig and Kligman's grade II-III).

In a 3-armed, multicentre, randomized, double-blind, vehicle-controlled study involving 91 patients with acne papulopustulosa, Plewig's grade II-III, evidence could be provided of a significant reduction of the propionibacteria as well as a subosuppressive effect (squalene reduction) under a combination of 1% chloramphenicol (CAS 56-75-7) and 0.5% pale sulfonated shale oil versus the alcoholic vehicle (1-2 ml twice daily). Likewise, monotherapy with chloramphenicol resulted in a significant reduction in bacteria compared to the vehicle. The combination therapy was superior to the monotherapy with regard to the sebosuppressive effects. Based on a kinetics test carried out for a total of 2 h, a clinically relevant percutaneous absorption of chloramphenicol was ruled out. The chloramphenicol serum level was between < 5.0 microgram/l to 180 microgram/l (average 25 micogram/l). This is important because with systemic application (peroral, i.v.), the therapeutic chloramphenicol level is > 25 mg/l (25,000 microgram 1). None of the blood count and serum parameters were pathologically changed in a clinically relevant way before and after the therapy. An induction of resistance against chloramphenicol in the propionibacteria could be excluded. No adverse events and side effects occurred. The topical therapy of acne papulopustulosa with chloramphenicol as a monosubstance or in combination with pale sulfonated shale oil represents an effective and safe local antibiotic treatment possibility.

Acne Vulgaris↗

Granulocyte colony-stimulating factor (G-CSF) treatment in a neutropenic leukemia patient with diffuse interstitial pulmonary infiltrates.

Adult respiratory distress syndrome (ARDS) in patients suffering from acute leukemia usually occurs during chemotherapy-induced neutropenia. In addition, intensified chemotherapy with high-dose cytosine arabinoside and mediastinal irradiation may contribute to the development of ARDS. This complication is usually refractory to conservative treatment with antibiotics, steroids, and mechanical ventilation. In this report, we describe a 25-year-old patient with acute lymphoblastic leukemia who developed ARDS during the phase of chemotherapy-induced neutropenia. Subcutaneous administration of granulocyte colony-stimulating factor (G-CSF) at doses of 300-600 micrograms/day led to a prompt increase of peripheral granulocyte counts. With resolution of neutropenia, respiratory function gradually improved, and mechanical ventilatory support was stopped after 2 weeks. From this observation we surmise that the application of G-CSF may be an effective therapeutic approach for preventing the fatal outcome of ARDS in leukemia patients with bone marrow aplasia.

Adult↗

The pathophysiology and clinical relevance of platelet heterogeneity.

Recent studies on platelet heterogeneity support the hypothesis that platelet production is regulated to maintain a constant functional platelet mass. In concept this form of regulation is analogous to the manner by which RBC production is controlled to maintain the oxygen-carrying capacity of blood. The platelet mass appears to correlate more closely with platelet function than the platelet count alone, since several factors in addition to the platelet count have been shown to influence the platelets' hemostatic function. These factors include platelet size, density, age, and previous hemostatic interactions. Application of these concepts to clinical problems has provided important insights into platelet physiology and reactivity. Failure to account for differences in platelet heterogeneity among individuals may introduce significant errors in the interpretation of data from laboratory and clinical investigations. However, despite advances, a number of practical issues remain to be resolved before measurements of platelet heterogeneity become accepted as routine clinical tests and are used in the diagnosis of pathologic states.

Animals↗

Treatment of cancer patients with recombinant interferon-gamma induces release of endogenous tumor necrosis factor-alpha.

STUDY OBJECTIVE: 1) to investigate serum levels of tumor necrosis factor-alpha in patients treated with recombinant interferon-gamma and 2) to relate changes in TNF serum levels to other biological responses observed during treatment with interferon gamma (IFN-gamma). PATIENTS: Five patients suffering from metastasizing renal cell carcinoma. INTERVENTION: Each patient received three treatment cycles of 10 micrograms, 100 micrograms and 500 micrograms IFN-gamma applied three times at weekly intervals. The treatment cycles were separated by a therapy free interval of two weeks. The order of dose levels was randomly assigned to each patient. MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor alpha (TNF-alpha), IFN-gamma and neopterin serum levels, monocyte counts in the peripheral blood and body temperature were measured immediately before and 4, 24, 48, 72, and 168 h after each application of IFN-gamma. Results indicated that elevated serum levels of TNF-alpha are induced by 100 micrograms and 500 micrograms IFN-gamma. Repeated application of the same dose led to downregulation of TNF release into the serum. Changes in TNF serum levels did not correlate with the magnitude of febrile reactions, neopterin production or IFN-gamma serum levels.

Aged↗

The applicability of the gland/wall ratio (Reid-Index) to clinicopathological correlation studies.

We studied at necropsy the bronchi of 49 subjects whose lung function has been measured during life. In each case the glands were examined in three bronchi by measuring the gland/wall ratio (Reid-Index) and by point-counting. The results of the two methods were compared: the data of the gland/wall ratio were normally distributed while those of the volume density established by point-counting were not. Gland/wall ratio and volume density of glands correlated moderately (RSp = 0.524). The function between them was not linear, in contrast with that between gland/wall ratio and gland thickness. The stereological background of these functions is discussed. In 34 subjects without restrictive lung disease FEV1 correlated inversely with the volume density of glands (RSp = -0.396), but not with the gland/wall ratio (Reid-Index)(RSp = -0.243). This discrepancy probably results from the different distribution of the data obtained by the two methods and from the non-linear function between them. These findings indicate that the gland/wall ratio (Reid-Index) is less applicable to clinicopathological correlations than the volume density of glands established by point-counting.

Adult↗

Bio-ALIRT biosurveillance detection algorithm evaluation.

INTRODUCTION: Early detection of disease outbreaks by a medical biosurveillance system relies on two major components: 1) the contribution of early and reliable data sources and 2) the sensitivity, specificity, and timeliness of biosurveillance detection algorithms. This paper describes an effort to assess leading detection algorithms by arranging a common challenge problem and providing a common data set. OBJECTIVES: The objectives of this study were to determine whether automated detection algorithms can reliably and quickly identify the onset of natural disease outbreaks that are surrogates for possible terrorist pathogen releases, and do so at acceptable false-alert rates (e.g., once every 2-6 weeks). METHODS: Historic de-identified data were obtained from five metropolitan areas over 23 months; these data included International Classification of Diseases, Ninth Revision (ICD-9) codes related to respiratory and gastrointestinal illness syndromes. An outbreak detection group identified and labeled two natural disease outbreaks in these data and provided them to analysts for training of detection algorithms. All outbreaks in the remaining test data were identified but not revealed to the detection groups until after their analyses. The algorithms established a probability of outbreak for each day's counts. The probability of outbreak was assessed as an "actual" alert for different false-alert rates. RESULTS: The best algorithms were able to detect all of the outbreaks at false-alert rates of one every 2-6 weeks. They were often able to detect for the same day human investigators had identified as the true start of the outbreak. CONCLUSIONS: Because minimal data exists for an actual biologic attack, determining how quickly an algorithm might detect such an attack is difficult. However, application of these algorithms in combination with other data-analysis methods to historic outbreak data indicates that biosurveillance techniques for analyzing syndrome counts can rapidly detect seasonal respiratory and gastrointestinal illness outbreaks. Further research is needed to assess the value of electronic data sources for predictive detection. In addition, simulations need to be developed and implemented to better characterize the size and type of biologic attack that can be detected by current methods by challenging them under different projected operational conditions.

Algorithms↗

Effect of daily floor treatment with sodium bisulfate on the fly population of horse stalls.

OBJECTIVE: To determine application rate and effectiveness of sodium bisulfate to decrease the fly population in a horse barn environment. SAMPLE POPULATION: 12 privately owned farms in southeastern Pennsylvania. PROCEDURE: Application rates of sodium bisulfate were approximately 2.3 kg/stall, 1.1 kg/stall, and 0.5 kg/stall. Two or 3 stalls were treated, and 1 or 2 stalls were not treated (control stalls) at each farm. Farm personnel applied sodium bisulfate in treated stalls daily for 7 days. Fly tapes were hung from the same site in treated and control stalls. After 24 hours, the fly tape was removed, flies adhering to the sticky surface were counted and recorded, and a new fly tape was hung. This procedure was repeated daily during each of the testing periods. RESULTS: Following the application of 2.3 kg of sodium bisulfate/stall, the numbers of flies collected on the fly tape were significantly decreased in treated stalls, compared with control stalls during the same time periods on 9 of the 12 farms evaluated. Following the application of 1.1 kg of sodium bisulfate/stall, fly numbers were significantly decreased in treated stalls on 6 of the 9 farms evaluated. Following the application of 0.5 kg of sodium bisulfate/stall, fly numbers were significantly decreased in the treated stalls on 3 of the 4 farms evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings suggest that sodium bisulfate would be effective for fly control in horse barns.

Animals↗

Experimental and numerical study of heterogeneous pressure-temperature-induced lethal and sublethal injury of Lactococcus lactis in a medium scale high-pressure autoclave.

The present contribution is dedicated to experimental and theoretical assessment of microbiological process heterogeneities of the high-pressure (HP) inactivation of Lactococcus lactis ssp. cremoris MG 1363. The inactivation kinetics are determined in dependence of pressure, process time, temperature and absence or presence of co-solutes in the buffer system namely 4 M sodium chloride and 1.5 M sucrose. The kinetic analysis is carried out in a 0.1-L autoclave in order to minimise thermal and convective effects. Upon these data, a deterministic inactivation model is formulated with the logistic equation. Its independent variables represent the counts of viable cells (viable but injured) and of the stress-resistant cells (viable and not injured). This model is then coupled to a thermo-fluiddynamical simulation method, high-pressure computer fluid dynamics technique (HP-CFD), which yields spatiotemporal temperature and flow fields occurring during the HP application inside any considered autoclave. Besides the thermo-fluiddynamic quantities, the coupled model predicts also the spatiotemporal distribution of both viable (VC) and stress-resistant cell counts (SRC). In order to assess the process non-uniformity of the microbial inactivation in a 3.3-L autoclave experimentally, microbial samples are placed at two distinct locations and are exposed to various process conditions. It can be shown with both, experimental and theoretical models that thermal heterogeneities induce process non-uniformities of more than one decimal power in the counts of the viable cells at the end of the treatment.

Biotechnology↗

Protection against radiation induced damage to spermatogenesis by Podophyllum hexandrum.

Aqueous extract of rhizome of Podophyllum hexandrum (RP-1) has been found to render protection against lethal whole body irradiation (10 Gy), damage to haemopoietic and gastrointestinal tissue etc. in mice. In order to assess its suitability from clinical point of view its effects were investigated on male germinal tissue in mice. Swiss albino strain 'A' male mice (10-12 weeks) were exposed to varied radiation doses (0.5, 2.0, 5.0 and 10 Gy) with and without 200 mg/kg b.w. of RP-1 and sacrificed at different time periods (10, 35 and 70 days) to collect the tissue. Administration of RP-1, 2 h before irradiation rendered a significant increase in the testis weight, repopulating tubules, resting primary spermatocytes, stem cell survival index, sperm counts and reduction in abnormalities of sperm morphology, at all the time periods studied here. RP-1 treatment alone did not generate any adverse effects. These results reveal that RP-1, if put to clinical application, will not be harmful to the testicular system.

Animals↗

Our experience in brachytherapy of certain non-cancerous diseases.

Brachytherapy of non-cancerous diseases has been used from the beginning of our century. The analgetic and antiinflammatory effects of gamma rays of the radionuclide Ra-226 has been used in the health resort in Jáchymov, located in Ore Mountains, Northern Bohemia since about 1911 in the therapy of patients hospitalized here with rheumatic diseases of joints, tendons and muscles, including the therapy of radical syndromes. The conditions for the therapy by this method are the age of above 42 years, normal blood count and certain other parameters commonly used in the non-cancer brachytherapy. The radiation dose depends on the degree of the involvement. The local single dose in our patients was of 1.8 to 3.5 Gy with an exposure time of 6 hours. In our work, we considered the degree of the damage to the skin on the irradiation site, after single dose, immediately after the application, as well as after the repeated irradiation in the course of several years. In persons followed, we also provided the examination of the blood count before and after irradiation. The results obtained demonstrated that the brachytherapy used in the health resort Jáchymov is safe and that it exerts no adverse effects on the patients submitted to it.

Brachytherapy↗

Chronic idiopathic thrombocytopenia treated with immunoglobulin.

Twenty five children with chronic idiopathic thrombocytopenic purpura followed from 6-96 months in 7 Italian paediatric departments were treated with high dose immunoglobulin according to a multicentre protocol. Positive responses were observed in 20 of 25 patients (80%) and negative responses in 5 of 25 (20%). On previous steroid treatment 7 of 10 positive responders were steroid resistant and 13 of 15 were steroid dependent. Within four weeks of beginning treatment 16 of 20 patients (80%) relapsed, while 4 of 20 (20%) maintained normal platelet values after 4-12 months' follow up. Statistical analysis of the platelet count on day five of treatment enabled us to divide positive responders into three groups: good, intermediate, and poor. The possible mode of action and clinical application of high dose immunoglobulin are discussed.

Adolescent↗

Simultaneous detection of two cell surface antigens by a red blood cell rosette-microsphere binding method, and its application to the study of multiple myeloma.

A sensitive method for the simultaneous detection of 2 cell surface antigens is described. One antigen is defined by a monoclonal antibody which is subsequently detected by binding bovine red blood cells coated with a suitable antibody. The second antigen is detected by antibody coated, small, highly fluorescent microspheres. The cells can be counted under visible light, or under low intensity visible light together with UV light and no switching of the illumination or filter systems is required to distinguish positive and negative cells. The application of the procedure to finding myeloma idiotype positive B cells in the blood of patients with multiple myeloma is described.

Animals↗

Advanced short-lived nuclide NAA with application in the life sciences.

A new technique for short-lived nuclide activation analysis has been developed that compensates the rapid radioactive decay during the counting period by simultaneous approach of the sample holder to the detector with a mechanical device, permitting prolongation of the counting time and reduction of the required complementary cyclic activation to avoid sample container damage. The operation of the analytical system is automated by a programmable logic controller (PLC). This improvement of short-lived nuclide activation analysis, providing a high throughput, is important in biological and environmental research, where often a large number of samples has to be analyzed for sufficient sampling statistics.

Animals↗

Simultaneous determination of the individual concentration gradients of two solute species in a centrifuged mixture: application to analytical ultracentrifugation.

A procedure for determining the absolute activity of 14C-labeled and 3H-labeled solutes in a mixture from the measured counts per minute in two scintillation energy windows is described. It is shown that the method described here provides a substantially more accurate determination of 3H activity in the presence of a larger 14C activity, and a more accurate determination of 14C activity in the presence of a larger 3H activity, than does the standard dual label analysis implemented in a Beckman LS 3801 scintillation counter. The new dual label procedure is combined with the automated fractionation procedure of Attri and Minton [(1986) Anal. Biochem. 152, 319-328] to permit the gradients of each of two differently radiolabeled solute species in a mixture to be individually determined following centrifugation. It is shown that the sedimentation coefficients of each of two differently labeled noninteracting proteins in a mixture may be readily determined in a sedimentation velocity experiment, and that the molecular weights of each of two such proteins in a mixture may be readily determined in a sedimentation equilibrium experiment.

Carbon Radioisotopes↗

Applications and limitations of blood eosinophilia for the diagnosis of acute cellular rejection in liver transplantation.

This study evaluates the predictive value of the blood eosinophil count in the diagnosis of acute cellular rejection, its value as a marker of response to treatment, the diagnostic use in a subgroup of patients with normal transaminases and compares blood eosinophilia in patients with and without hepatitis C virus infection. A consecutive cohort of 101 liver transplant patients, 275 liver biopsies, and blood eosinophils recorded on the day or one day before biopsy were analyzed. An elevated eosinophil count has a positive predictive value for acute cellular rejection of 82%. A normal eosinophil count excludes moderate/severe rejection with a predictive value of 86%. The eosinophil count decreases in 69% of patients following treatment of acute cellular rejection with corticosteroids irrespective of treatment outcome. Acute cellular rejection in the presence of an elevated eosinophil count occurs significantly less often (p = 0.007) in patients with hepatitis C virus. An elevated eosinophil count is a valuable marker of acute cellular rejection. However, blood eosinophil levels should not be used to predict acute cellular rejection following treatment with corticosteroids. Blood eosinophilia, seen less often in patients with hepatitis C virus, may reflect an over-diagnosis of acute cellular rejection in these patients.

Adult↗

[The progresses in the determination of blood monocytosis and its perspectives of clinical application in pathology].

Automated cell counters have allowed the reproducible analysis of the 5 leucocyte populations (neutrophils, eosinophils, basophils, lymphocytes and monocytes). Determination of the monocyte count by classical microscopic analysis can be inaccurate. We have compared the automated monocyte count from the coulter STKS (program 1F) with counts obtained by microscopic analysis of 1000 leucocytes and by flow cytometric analysis of cells stained simultaneously with a pan-leucocyte and a monocyte-specific antibody. The values provided by the coulter STKS are sufficiently precise to recommend the routine clinical use of this automated counter.

Female↗

Microtechnique for quantitative platelet isolation from blood enabling electronic counting and sizing of animal and human platelets.

A technique for rapidly separating platelets from small quantities of whole blood is described. The isolation method allowed for counting and sizing platelets by electronic means, and counts with this new method were closely correlated with those obtained by phase microscopy. Platelet sizing was possible because of the inert and isotonic nature of the density-gradient medium used in the procedure. The technique was applicable to samples of blood from persons, horses, cattle, sheep, goats, pigs, dogs, mice, rats, guinea pigs, and rabbits. The isolation of platelets from whole blood of various species of animals was necessary for electronic counting because of the great variation in sizes of platelets and erythrocytes and the variable sedimentation properties of animal blood.

Adult↗