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Biomedical subjects

W Bayer

Publications and source records attributed to W Bayer.

16 recordsLinked to original sources
PubMed2006

Synergy between expression of fusogenic membrane proteins, chemotherapy and facultative virotherapy in colorectal cancer.

Using Chou-Talalay median effect analysis, we demonstrated in permanent and short-term cultures of colorectal cancer cells that the expression of measles virus fusogenic membrane glycoproteins (FMGs) in combination with chemotherapy often causes over most of the cytotoxic dose range synergistic cell killing. In this combined treatment, we observed strongly enhanced annexin V binding and caspase-3/7 activity when compared to single-agent treatment. Furthermore, we showed increased expression of heat-shock protein (Hsp)70 and Hsp90alpha, but not of Hsp60. In a subcutaneous HT-29 colorectal xenograft model, we demonstrated that the administration of a replication-defective adenoviral or herpes simplex virus (HSV) amplicon vector (Ad.H/F or HSV.H/F) encoding tumor-restricted FMG in combination with FOLFOX significantly enhanced treatment outcome when compared to treatment with each compound individually. To increase the fraction of tumor cells expressing the FMG, we trans-complemented the Ad.H/F and HSV.H/F vector with the respective oncolytic replication-restricted adenovirus Ad.COXDeltaMK or HSV-1 G47Delta vector. At the end of the observation period (day 100), eight out of 10 animals that received G47Delta, HSV.H/F and FOLFOX were alive and tumor free. Administration of the analogous adenovirus-based regimen resulted in four out of 10 long-term survivors. We demonstrated that the expression of FMG in combination with chemotherapy can significantly enhance treatment outcome, which is further enhanced by combination with trans-complementing oncolytic vectors.

Adenoviridae↗
PubMed1993

The post-antibiotic effect of antimicrobial combinations in a neutropenic murine thigh infection model.

The post-antibiotic effect (PAE) may allow for more widely spaced dosing of antibiotics than is currently employed without loss of efficacy. Antimicrobial combinations are widely used in clinical medicine. However, dosing schedules are usually based on pharmacological profiles of the drugs used alone. Previously we have demonstrated significant prolongation of the PAE induced by antimicrobial combinations in vitro as compared to PAEs induced by the agents alone. We examined this issue further in vivo in a neutropenic mouse thigh infection model, by exposing Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae to several antimicrobials, either singly or in combination. The PAE in vivo was defined as the difference in time needed for the organisms in the treated animals to grow 1 log10 as compared with controls after serum drug concentrations had fallen below the MIC. Drug concentrations exceeded the MIC for 1.2-3.2 h, but bactericidal activity occurred mainly during the first hour. When the agents were used singly a negative PAE was produced by ceftazidime against P. aeruginosa, a PAE of approximately 0 h by imipenem against E. coli and K. pneumoniae, a PAE of 2-4 h by cefazolin against S. aureus, gentamicin against E. coli and K. pneumoniae, and imipenem and tobramycin against P. aeruginosa, and a PAE of 6-7 h by gentamicin against S. aureus and rifampicin against P. aeruginosa. The beta-lactam/aminoglycoside combinations when used against S. aureus and P. aeruginosa prolonged the PAE by 1.0-3.3 h, compared with the longer of the individual drug PAEs, but no prolongation was observed against E. coli and K. pneumoniae. Ceftazidime reduced the PAE when used with tobramycin against P. aeruginosa. The long PAE of rifampicin against P. aeruginosa was 'carried over' to the combination, thus prolonging the growth suppression achieved by imipenem and tobramycin alone or in combination by 5.5-8.0 h. This effect on the PAE was additive only, and synergy was not observed. In conclusion, a potentially significant prolongation of the PAE by combination of drugs was observed in vivo, but only if both (or all) agents induced a PAE when used alone. The impact of this observation needs to be examined further in studies involving multiple and different dosing regimens in an infection model.

Animals↗
PubMed1993

The effect of fine-needle aspiration biopsy on the thyroid scan.

Fine-needle aspiration biopsy (FNAB) is the most sensitive and specific procedure in diagnosing benign from malignant thyroid nodular disease. The effects of a FNAB on the thyroid scan, however, have never been studied. This assumes importance because a hot nodule on scan has been advocated as useful to differentiate certain benign from malignant follicular neoplasms. Thyroid scans were performed before and after FNAB on 11 patients with nodular thyroid disease and an area of normal or increased uptake either in the nodule or in a contralateral enlarged lobe to determine if the biopsy changed the pattern of isotope uptake. For this study, biopsies were done in the area of normal or increased uptake. In two patients, there was a reduction in isotope concentration in three nodules after FNAB, whereas no change was demonstrable in nine other patients. Review of the literature revealed a number of prior reports of hemorrhage, necrosis, or infarction of thyroid nodules after FNAB. Based on these data and the demonstration of a change in scan pattern in a patient following FNAB, it is concluded that FNAB may decrease the isotope uptake in thyroid nodules; therefore, the concept of clinical judgments being based on the scan pattern after FNAB should be reevaluated.

Adult↗
PubMed1989

Serum selenium levels in patients with malignant melanoma.

The incidence of malignant melanoma of the skin has increased rapidly among white people during the last decade. Although the pathogenesis of malignant melanoma is not clear, epidemiologic data and experimental work indicates that ultraviolet (UV) radiation plays a critical role in tumorigenesis. Recent data implicate peroxidative reactions in UV-carcinogenesis and clearly demonstrate that selenium (Se) confers protection, in part by inducing cellular-free radical scavenging systems and by enhancing peroxide breakdown, thus enhancing the capacity of the cell to cope with oxidant stress. With this in mind, we investigated the Se status of 101 patients with malignant melanoma. Our study revealed significantly lower Se levels in the sera of melanoma patients than of controls. Although patients in all clinical stages had lower Se levels than the controls, patients in stage III (disseminated melanoma) had the lowest levels. Separate analysis of histogenetic subtypes of melanoma revealed that lentigo maligna melanoma (LMM) and superficial spreading melanoma (SSM) had the strongest association with depressed Se serum levels. Our results, showing for the first time that malignant melanoma is associated with low Se concentrations, are consistent with results of epidemiologic studies showing an inverse correlation between serum Se levels and certain cancers.

Adult↗
PubMed1985

Pharmacokinetics of intravenous ceftizoxime in patients on continuous ambulatory peritoneal dialysis.

The pharmacokinetics of ceftizoxime (CZM) were determined in 16 non-infected CAPD patients. Patients received either 500 mg or 1000 mg CZM by i.v. bolus. The dialysate exchange volume was 2 l. Serum CZM concentrations at 10 min were 69.7 +/- 19.7 micrograms/ml (1000 mg dose) and 39.2 +/- 8.4 micrograms/ml (500 mg dose), and declined to 33.7 +/- 13.9 micrograms/ml and 16.9 +/- 3.2 micrograms/ml respectively at 360 min. Dialysate CZM levels at 10 and 360 min were 1.8 +/- 1.3 and 19.9 +/- 6.6 micrograms/ml respectively (1000 mg dose) and 1.4 +/- 0.9 and 12.6 +/- 3.5 micrograms/ml (500 mg dose). The half-time of CZM was 14.1 +/- 4.6 h. Peritoneal clearance of CZM was low and equilibrium was not achieved in 6 h. However peritoneal CZM concentrations were adequate within 1 h for the treatment of most organisms which cause CAPD-related peritonitis.

Adult↗
PubMed1984

Seasonal pattern of tick load in Bunaji cattle in the subhumid zone of Nigeria.

The seasonal pattern of tick load on Bunaji cattle under traditional management in northern Nigeria was observed over 12 months to investigate the possibilities of strategic use of acaricide. Ticks were removed 2-3 times weekly by hand from 16 animals, counted and the species determined. Tick load was low in the dry season (2-5 ticks per animal per week), increased after the onset of the first scattered rains, reached a peak (40 ticks per animal per week) 1 month after the beginning of the heavy rains, and declined thereafter. The dominant tick species was Amblyomma variegatum; other species found were Boophilus spp., Rhipicephalus spp. and Hyalomma spp. The low level of tick load compared with data from literature and from crossbred (Friesian-Bunaji) cattle kept in the study area suggests high tick resistance in Bunaji cattle. A biologically feasible method of controlling ticks in indigenous cattle would be twice weekly spraying with acaricide during only 2 months of the year in the early wet season to break the pronounced peak in the tick load. However, hand spraying offers no advantage over hand removal of ticks in terms of saving labour. The main advantage of strategic spraying lies in more thorough removal of ticks and possibly prevention of dermatophilosis at a lower cost than year-round use of acaricide. Knowledge of the seasonal pattern of tick load is also valuable for planning the introduction of selected stock with higher genetic potential, but higher susceptibility to tick-borne diseases than exhibited by Bunaji cattle.

Animals↗
PubMed1983

Hyperthermia-induced intracellular ionic level changes in tumor cells.

The intracellular content of potassium (K) ions in P815 cells decreases when the media pH is lowered, and it increases when media pH is raised. The determination of the ion content therefore requires accurate control of the medium pH. The K ion content measured both by the flame emission method and by the K analog. 86Rb, exhibits a decline when the cells are incubated at 43 degrees C at a fixed pH chosen between 7.4 and 6.7. The chloride content also decreases while the sodium content does not change by a significant amount. Under the same hyperthermic conditions the intracellular pH decreases by a fraction of a pH unit. Simultaneously, the cell water volume increases by 20%, as measured by tritiated water. In the final analysis, hyperthermia produces an apparent deficit in the cellular osmolarity. A possible explanation is given.

Animals↗
PubMed1982

Convulsive syncope in blood donors.

Syncope with and without convulsion was studied in unselected blood donors in a community blood center. Convulsive syncope occurred in 0.03% of all blood donors and was more commonly observed when nursing personnel were alerted to its possible occurrence. It was more common in men. Although tonic extensor spasm was the most common convwithout convulsion was studied in unselected blood donors in a community blood center. Convulsive syncope occurred in 0.03% of all blood donors and was more commonly observed when nursing personnel were alerted to its possible occurrence. It was more common in men. Although tonic extensor spasm was the most common convwithout convulsion was studied in unselected blood donors in a community blood center. Convulsive syncope occurred in 0.03% of all blood donors and was more commonly observed when nursing personnel were alerted to its possible occurrence. It was more common in men. Although tonic extensor spasm was the most common convulsive movement, other complex convulsive phenomena occurred, some simulating epileptic seizure. No statistical difference in changes of pulse or blood pressure was found between subjects with convulsive versus nonconvulsive syncope. Similarly, no difference was found between subjects with tonic spasm and those with other convulsive phenomena, nor between those with "early" and those with "delayed" reactions. Marked individual variation may exist in the susceptibility of the central nervous system to ischemia. Some individuals appear to be predisposed to development of seizures in situations of global cerebral ischemia such as occur in hypotension and bradycardia.

Blood Donors↗
PubMedDate not supplied

Regional pattern of hippocampus and corpus callosum atrophy in Alzheimer's disease in relation to dementia severity: evidence for early neocortical degeneration.

We used volumetric MRI and analysis of areas under receiver operating characteristic (ROC) curves to directly compare the extent of hippocampus-amygdala formation (HAF) and corpus callosum atrophy in patients with Alzheimer's disease (AD) in different clinical stages of dementia. Based on neuropathological studies, we hypothesized that HAF atrophy, representing allocortical neuronal degeneration, would precede atrophy of corpus callosum, representing loss of neocortical association neurons, in early AD. HAF and corpus callosum sizes were significantly reduced in 27 AD patients (37% and 16%, respectively) compared to 28 healthy controls. In mildly- and moderately-demented AD patients, the ROC derived index of atrophy was greater for HAF volume than for total corpus callosum area. The index of atrophy of posterior corpus callosum was not significantly different from HAF at mild, moderate or severe stages of dementia. In conclusion, these findings suggest a characteristic regional pattern of allocortical and neocortical neurodegeneraton in AD. Our data indicate that neuronal loss in parietotemporal cortex (represented by atrophy of corpus callosum splenium) may occur simultaneously with allocortical neurodegeneration in mild AD. Moreover, ROC analysis may provide a statistical framework to determine atrophy patterns of different brain structures in neurodegenerative diseases in vivo.

Aged↗
PubMedDate not supplied

Effect of fine needle aspiration biopsy on the histology of thyroid neoplasms.

We evaluated the effect of fine needle aspiration biopsy (FNAB) upon the histology of thyroid adenoma and differentiated thyroid carcinoma. When surgery was performed within three months of FNAB, infarction was found histologically in 8/82 (9.8%) of the tumors. It was extensive in four patients, with one patient having no residual neoplastic cells identifiable within the nodule. No infarction was seen in the histologic specimens from patients with similar pathology whose surgery was performed without prior FNAB. These findings confirm previous reports that infarction may be caused by FNAB and can be so extensive as to interfere with the histologic diagnosis.

Adenocarcinoma↗