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P Evers

Publications and source records attributed to P Evers.

At least 19 recordsLinked to original sources

Antigen retrieval in formaldehyde-fixed human brain tissue.

Microwave-stimulated antigen retrieval has become a widely accepted method in both pathology and research laboratories. Since the introduction of the method in 1991, many groups have tried to optimize and standardize it. This review describes the present state of the art. A standard method for microwave-stimulated antigen retrieval in formaldehyde-fixed paraffin-embedded and nonembedded tissue is presented that results, in general, in very good staining for antibodies used in neuroscience. However, there are still a few antigens that are retrieved not at all or not in an optimal manner. Factors of importance for microwave antigen retrieval are the pH of the retrieval solution and, related to the pH, the temperature and duration of heating. These factors are discussed.

Antigens↗

An optimal antigen retrieval method suitable for different antibodies on human brain tissue stored for several years in formaldehyde fixative.

In the last 5 years the microwave oven has become a widely accepted apparatus for retrieving all kinds of antigens that are masked by prolonged formaldehyde fixation. However, it has so far not been possible to obtain good results for all the antigens we were interested in with just one method. This study offers a solution for this problem. We tested Tris buffered saline (TBS) pH 8-10 in order to see whether a microwave (MW) pretreatment in a solution with a high pH works on the antigens that have our particular interest: MAP-2, non-phosphorylated part of the neurofilament (SMI-32, SMI-311), phosphorylated part of the neurofilament (SMI-312) and the calcium binding proteins Calbindin D28-K, Parvalbumin and Calretinin. Furthermore we checked whether or not a lower temperature of 90 degrees C (instead of boiling the tissue) could be used to achieve the same good staining results. These tests showed that an MW pretreatment in TBS pH 9.0 at full power (boiling) gave the best results. Pretreatment at a lower temperature gave also good results for most (but not all) antibodies when the irradiation time was prolonged to 30 min. The optimal antigen retrieval method also improved the quality of staining with an antibody against neuropeptide Y (NPY), for which, until now, no antigen retrieval appeared to be necessary, even after a long duration of fixation.

Adolescent↗

Laminar distribution of neuropeptide Y-immunoreactive neurons in human prefrontal cortex during development.

Neuropeptide Y (NPY) is present in neurons of the adult human cerebral cortex. In view of the reported roles of NPY in the central nervous system in health and during certain disease conditions, we have studied normal development of NPY immunoreactivity (-ir) in the human prefrontal cortex (PFC), Brodmann areas 9 and 46. Twenty-six specimens ranging from the ages of 14 postovulatory weeks to 34 years exhibited patterns that revealed six periods in the development of the laminar distribution and density of NPY-ir neurons. Changes during prenatal and perinatal periods reflect the onset, development, and resolution of the transient fetal telencephalic compartments, including the subplate zone, in which NPY-ir neurons are especially abundant. Before the age of 1 year, the majority of NPY-ir neurons were found in the subplate zone, whereas, after 1 year, the majority were seen in the cortical layers. This is in contrast with the human visual cortex, where the majority of NPY-ir neurons were still located in the white matter. The density of cortical NPY-ir neurons increased in the fifth developmental period (ages 4-7 years), coinciding with the increase of cortical volume and marked progression of cognitive functions. The adult pattern of a relatively low density of cortical NPY-ir neurons was reached in period 6 (from about 8 years), when individual variation also became apparent. Our data point to a protracted maturation of NPY-ir in the human PFC and to different distribution patterns of NPY-ir neurons in different cortical areas.

Adolescent↗

Long-term results of treatment of traumatic coxofemoral joint dislocation in dogs: 64 cases (1973-1992).

OBJECTIVE: To determine long-term results of various treatments for traumatic coxofemoral joint dislocation in dogs. DESIGN: Retrospective case series. ANIMALS: 64 dogs that underwent closed reduction and bandage stabilization, extracapsular suture stabilization, transacetabular pinning, toggle pinning, DeVita pinning, or femoral head and neck excision. PROCEDURE: Follow-up evaluations included owner evaluation (64 dogs), physical evaluation (23), and radiography (19). Follow-up time ranged from 8 to 156 months. RESULTS: Owner evaluation scores after closed reduction were significantly better than scores after DeVita pinning, extracapsular suture stabilization, and femoral head and neck excision. On physical examination, 6 of 23 dogs were lame on the side of the previous dislocation. Signs of pain and crepitation were evident during palpation of 12 and 8 of 25 joints, respectively. Thirteen of 21 joints had radiographic evidence of degenerative joint disease. There was a greater progression of degenerative joint disease in previously dislocated joints than in unaffected joints. There were not any significant differences between treatments in regard to results of physical and radiographic evaluation. Time between trauma and treatment and existence of concomitant injuries did not influence follow-up results, but there was a significant association between body weight and radiographic evaluation score. CLINICAL IMPLICATIONS: Concomitant injuries do not appear to justify a worse prognosis in dogs with traumatic coxofemoral joint dislocation, nor does a delay in treatment of > 3 days. Gait abnormalities and degenerative joint disease might develop in the long term. Proper body weight should be maintained regardless of treatment.

Animals↗

Effects of microwave pretreatment on immunocytochemical staining of vibratome sections and tissue blocks of human cerebral cortex stored in formaldehyde fixative for long periods.

The effects of the microwave antigen-retrieval method were investigated for five antibodies commonly used in neurosciences, i.e., Parvalbumin, Calbindin D28-K, MAP-2, MAP-5 and SMI-32. Immunocytochemical stainings were performed on free-floating vibratome sections of tissue which had been stored in fixative for as long as 10 months to compare the effects of microwave treatment in one of the different metal solutions or in distilled water. Microwave treatment of free-floating vibratome sections led to a severe wrinkling of the sections. Therefore the possibility of pretreatment of a thick tissue slice before vibratome sectioning was investigated. We conclude that microwave pretreatment of tissue slices in an aluminium chloride solution is the preferable antigen-retrieval procedure for the examined antibody staining when the immunocytochemical staining is lost or markedly reduced after storage in formaldehyde fixative for a long period. In particular SMI-32 and MAP-2, but also Parvalbumin staining, improved enormously after such a pretreatment.

Adult↗

Microwave-stimulated antigen retrieval is pH and temperature dependent.

The effects of the pH of solutions used in microwave-stimulated antigen retrieval were investigated for two antibodies commonly used in neurosciences, MAP-2 and SMI-32. A prolonged fixation time (longer than 1 week) prevents good immunohistochemical staining of these and many other antigens in paraffin and vibratome sections. On human brain tissue stored for 17 months in formaldehyde, the effects of different solutions during microwave treatment were compared, i.e., 4% aluminum chloride (pH 2.75), 0.1 N hydrochloric acid (pH 0.98), and citrate buffers (pH 2.5, 4.5, 6.0), together with the influence of temperature and microwave irradiation. We conclude that the pH and temperature of the solutions and the irradiation time are of great importance for the retrieval of antigens, but in a different way for the two antibodies studied. The SMI-32 staining results are optimal with citrate buffer at pH 2.5 and 2-hr irradiation at 90 degrees C, whereas MAP-2 staining results are optimal with citrate buffer at pH 4.5 and 10-min full-power irradiation. In the other conditions the staining is less intensive or less homogeneously distributed over the section.

Antibodies, Monoclonal↗

A comparison of 2 modes of administration of recombinant interleukin-2: continuous intravenous infusion alone versus subcutaneous administration plus interferon alpha in patients with advanced renal cell carcinoma.

PURPOSE: To compare 2 treatment modalities with recombinant Interleukin-2 (rIL-2) for patients with advanced Renal Cell carcinoma (RCC): continuous intravenous infusion (CIV) alone versus subcutaneous (s/c) rIL-2 + Interferon-alpha (IFN-alpha). PATIENTS AND METHODS: Data have been collected on 425 patients with RCC, treated CIV rIL-2 alone, (225 patients), or rIL-2 by the s/c route (200 patients). Patients receiving s/c rIL-2 also received s/c IFN-alpha both drugs being administered on an outpatient basis. Patients receiving CIV rIL-2 were treated as inpatients. Patient eligibility criteria were similar on all studies, and included patients with progressive, advanced disease, but with an ambulatory performance status. RESULTS: The overall response rate for the CIV schedules was not significantly different from the s/c regimens: 15% (95% confidence limits (CL) 10-20%) vs 20% (95%CL 14-26%) with 4% CR in both approaches. Durable responses were seen in both CIV and s/c schedules and there was no evidence of a significant difference in survival in multivariate analysis. There was however an important shift in the toxicity profile. The s/c regimens do not induce a clinically detectable capillary leak syndrome, which is the dose limiting toxicity for CIV regimens. CONCLUSION: Although the introduction of CIV regimens of rIL-2 was a major step forward compared to high-dose bolus, because most patients could be treated in a normal oncology ward, the s/c schedule of rIL-2 + IFN-alpha offers the possibility of outpatient (home) therapy, with no evidence of a reduction in efficacy.

Adult↗

Continuous infusion of recombinant interleukin-2 with or without autologous lymphokine activated killer cells for the treatment of advanced renal cell carcinoma.

Data have been analysed for 327 patients with advanced renal cell carcinoma receiving a continuous infusion of recombinant interleukin 2 (rIL-2) alone (225 patients) or rIL-2 plus lymphokine activated killer (LAK) cells (102) on a normal oncology ward. Eligibility criteria were uniform across protocols, all patients having advanced progressive disease, but with an ambulatory performance status. The baseline characteristics of patients receiving rIL-2 alone did not differ significantly from those receiving LAK, with the exception that the LAK treated patients had a better performance status. Despite similar treatment intensity, toxicity was more severe in the patients receiving LAK. The addition of LAK did not lead to higher response rates or to prolonged response duration, progression-free survival or survival. This review confirms the activity of rIL-2 for the treatment of advanced renal cell carcinoma and demonstrates that the addition of LAK cells does not lead to increased efficacy.

Adult↗

Propolis allergy (IV). Studies with further sensitizers from propolis and constituents common to propolis, poplar buds and balsam of Peru.

26 different compounds have been investigated experimentally for their sensitizing capacity in guinea pigs. 19 of these occur in propolis as well as in poplar bud exudates, and 14 of them are also found in balsam of Peru. 4 caffeates and benzyl isoferulate were found to be strong sensitizers. 7 compounds were moderate, and 13 compounds showed only weak sensitizing potency. Methyl cinnamate was negative. Patch tests in 11 propolis-sensitive patients once more revealed 3-methyl-2-butenyl caffeate and phenylethyl caffeate as the major sensitizers. In addition to the 8 compounds already known to occur in propolis as well as in balsam of Peru, we detected 5 further substances that both materials have in common. Among these, benzyl isoferulate is considered a noteworthy sensitizer. Coniferyl benzoate, which was shown to be a moderate sensitizer, is present in fresh samples of balsam of Peru, while in propolis it has been detected only once so far. The flavonoid aglycones occurring in poplar bud exudates, and hence also in propolis, are weak sensitizers which play only a minor role in propolis hypersensitivity.

Allergens↗

The development of neutralizing antibodies in a patient receiving subcutaneous recombinant and natural interleukin-2.

Systemic administration of interleukin-2 (IL-2) in humans may induce antibodies specific to IL-2. The case is reported of a patient with metastatic rectal carcinoma who was treated with long-term subcutaneous IL-2 and a combination of subcutaneous IL-2 and interferon-alpha 2b (IFN-alpha 2b). This patient developed nonneutralizing and neutralizing anti-IL-2 antibodies recognizing both the recombinant and natural cytokine. Detectable serum levels of neutralizing antibodies were accompanied by the inhibition of immune responsiveness to systemic IL-2 in vivo.

Antibodies↗

Assessment of body composition by bioelectrical impedance in a population aged greater than 60 y.

Body composition was measured in a group of 35 healthy men and 37 healthy women aged 60-83 y. Body mass index (BMI) in men was 25.0 +/- 2.2 kg/m2 (means +/- SD) and in women, 25.9 +/- 3.2 kg/m2. BMI was low in relation to body fat percentage as determined by skinfold-thickness measurements or densitometry in comparison with the relation found in younger adults. Mean body fat percentage of the male subjects (aged 70.4 +/- 5.2 y) as determined by densitometry was 31.0 +/- 4.5%, whereas in women (aged 68.0 +/- 5.2 y) it was 43.9 +/- 4.3%. Body impedance correlated with fat-free mass (FFM). The best prediction formulas for the FFM from body impedance and anthropometric variables were 1) FFM (kg) = (0.671 x 10(4) x H2/R) + 3.1S + 3.9 where H is body height (m), R is resistance (omega), and S is gender (females, 0; males, 1) (r = 0.94; SEE = 3.1 kg) and 2) FFM (kg) = (0.360 x 10(4) x H2/R) + 0.359BW + 4.5S - 20T + 7.0 where BW is body weight (kg) and T is thigh circumference (m) (r = 0.96; SEE = 2.5 kg). The prediction equations from the literature, generally determined in younger populations, overestimated FFM in elderly subjects by approximately 6 kg and are not applicable to elderly subjects.

Adipose Tissue↗

[The diagnosis of adrenal cortical function in animals using hormone analysis].

This paper describes the use of hormone analysis in the diagnosis of adrenal cortex dysfunction in the dog, cat and horse. Analytical problems concerning the determination of corticosteroid levels are discussed and the pathology of adrenal dysfunction is briefly presented. The paper focuses on the problems in establishing physiological norms for adrenal function based on the established assays. Own experiences and other reported data are referred to.

Adrenal Cortex Diseases↗

Subcutaneous interleukin-2 and interferon-alpha 2b in patients with metastatic renal cell cancer: the German outpatient experience.

A phase II clinical trial was conducted using subcutaneous recombinant human interleukin-2 (rIL-2, EuroCetus) and subcutaneous interferon-alpha 2b (rIFN-alpha 2b, Essex) in patients with advanced cancer. Safety and tolerance of this outpatient regimen were assessed in 17 patients with progressive metastatic renal carcinoma, 14 of whom were evaluable for clinical response to combined rIL-2 and rIFN-alpha 2b. In this study, rIL-2 was administered every 12 hours, at 1.5 million (Cetus) U/m2 on days 1 and 2, followed by 0.3 million U/m2 5 days per week for 6 consecutive weeks. Concomitantly, rIFN-alpha 2b was given as 5 million U/m2 three times weekly for 6 consecutive weeks. Patients presenting with stable or regressive disease after 6 weeks of rIL-2 and rIFN-alpha 2b (11 of 14) were scheduled to repeat combination therapy. After one treatment cycle, five of 14 patients presented with partial remission; two of these patients achieved complete regression of metastatic lesions. After therapy, six patients have been in stable disease for up to 8 months. toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (World Health Organization criteria) fevers, chills, malaise, nausea and/or vomiting, and anorexia in 70% to 100% of patients treated. After 6 weeks of rIL-2 and rIFN-alpha 2b, laboratory evidence of treatment-related hypothyroidism and hyperthyroidism was obtained in one and four patients, respectively. Immunogenicity of sc rIL-2 was mostly limited to the development of nonneutralizing antibodies that occurred in approximately 40% of patients. None of the patients exhibited antibodies specific to rIFN-alpha 2b.

Ambulatory Care↗

Low-dose subcutaneous recombinant interleukin-2 in advanced human malignancy: a phase II outpatient study.

Recombinant interleukin-2 (rIL-2; EuroCetus, Amsterdam, Netherlands) was studied in an outpatient phase II trial in 14 patients with progressive metastatic renal carcinoma, malignant melanoma, and colorectal cancer. Escalating doses of rIL-2 were administered as subcutaneous bolus every 12 hours, starting at 0.3 million U/m2/d. A 100% dose increase occurred at weekly intervals, up to a maximum of 2.4 million U/m2/d. Responding patients or patients with stable disease after 4 weeks of rIL-2 (n = 9) were continued on maintenance therapy at 1.8 million U/m2 of rIL-2 administered once weekly. After 12 weeks of therapy, one renal cell cancer patient had a partial regression in lung metastases. Bolus injection of rIL-2 (1.2 million U/m2) resulted in peak serum levels of 25 to 30 U/ml. Toxicity of this regimen was moderate, with local inflammation at the injection sites, grade I-II (World Health Organization) malaise, nausea and/or vomiting, and fevers in 70% to 100% of patients treated. Thyroid dysfunction was observed in 10 patients receiving subcutaneous rIL-2; four of these patients had laboratory evidence of hyperthyroidism, and one had hypothyroidism. rIL-2-induced toxicity reversed spontaneously after cessation of treatment. In all patients receiving rIL-2, a dose-dependent increase in peripheral blood lymphocyte and eosinophil counts was noted, with a mean of 2.6 and 3.8 x 1,000/microliters after 4 weeks of therapy; mean lymphocyte and eosinophil counts were measured at 2.0 and 2.4 x 1,000/microliters in patients who received prior high-dose chemotherapy, compared with 3.2 and 5.1 x 1,000/microliters in those who did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Anorexia↗

Lesions of the SDN-POA inhibit sexual behavior of male Wistar rats.

Discrete bilateral lesions in the SDN-POA of sexually naive adult male rats were found to decrease the number of animals ejaculating and/or to increase latencies to the first mount, intromission and ejaculation. The deleterious effects of the lesions disappeared after 4 tests for sexual behavior but were reinstated when the males were tested under suboptimal conditions, i.e., when they were tested with a marginally receptive female or when they had only limited access to the stimulus female. It was subsequently shown that males with a bilaterally lesioned SDN-POA still showed an increase in plasma testosterone. LH and prolactin levels in response to sexual stimulation. Effects of the lesions on scent marking were not found. Together with previous data indicating that SDN-POA-lesions disrupt masculine sexual behavior in females, these data are taken as evidence that the SDN-POA plays a role in the regulation of masculine sexual behavior. The data further suggest that previously reported negative results of SDN-POA-lesions on masculine sexual behavior in male rats might be attributed to the use of sexually experienced instead of sexually inexperienced animals.

Animals↗

Body mass index as a measure of body fatness in the elderly.

Body composition was assessed in a group of 35 apparently health elderly males and 37 elderly females, aged 60-83 years, by means of anthropometry and densitometry. Mean body mass index (BMI) of the males was 25.0 +/- 2.2 kg/m2 and of the females 25.9 +/- 3.2 kg/m2, which indicates normal weight to only minor overweight. Body fat as assessed by densitometry was 31 per cent in men and 44 per cent in women, a rather high value, especially when compared to the rather low BMI. Body fat percentage as calculated from the sum of four skinfolds (bicipitalis, tricipitalis, subscapularis and supra-iliacalis) using regression equations from the literature was 27.9 +/- 2.5 per cent and 38.7 +/- 3.2 per cent for men and women respectively. These values are probably an underestimation of the body fat, due to a higher proportion of internal fat in elderly subjects, which is not measured by skinfolds. Body fat percentage as determined by the BMI has an estimation error of about 4 per cent when derived from sex- and age-specific regression equations. The body fat percentage as predicted from skinfold thicknesses had a comparable error of estimate. These prediction errors in the body fat percentage in the elderly are comparable with the prediction errors found in young and middle-aged subjects as reported in the literature.

Adipose Tissue↗