Biomedical subjects

C Binder

Publications and source records attributed to C Binder.

228 records · Page 13Linked to original sources

PubMedDate not supplied

Think before you act: a national survey of interhospital transfer policies and practices.

INTRODUCTION: As health care evolves, air medical program (AMP) interhospital transfers will come under increasing scrutiny. The object of this study was to evaluate various components of the interhospital transfer policies of AMPs across the country. METHODS: A structured telephone interview of the chief flight nurse (CFN) or administrator of 90 geographically selected AMPs was conducted by a college-educated research assistant using a scripted questionnaire. RESULTS: Seventy-seven (86%) of the AMPs contacted agreed to answer the questionnaire. CFN or administrator unavailability was the reason for nonresponse. The mean number of flights performed per year was 1046: 29% scence and 71% interhospital missions. Mission profile ranged from fixed-wing (19), rotor-wing (45), and both (13). Forty-five percent of respondents require prior administrative approval and 31% require prior medical approval before accepting an interhospital mission. Financial approval or long distance transport was the most common reason for requiring approval. Ninety-four percent of programs transferred patients to facilities other than the AMPs' host hospital; two-thirds of these programs required medical (30%) or administrative (35%) authorization before accepting missions. CONCLUSION: This survey indicates that most AMPs use some form of screening mechanism for interhospital flight requests. With managed care requiring health care delivery systems to examine the use of resources, AMPs should continue to stay ahead of trends that affect the industry.

Air Ambulances↗

PubMedDate not supplied

Insulin antibodies in diabetic children before treatment: a marker for islet B-cell destruction?

Insulin antibodies were measured in the sera of 28 newly diagnosed diabetic children (age 8.0 +/- 4.0 (+/- SD) years) prior to insulin therapy and after 3, 6, 9, and 12 months. The levels at diagnosis and after 12 months were compared to endogenous insulin production at onset and after 12 to 14 months. Endogenous insulin production was evaluated through the measurement of 24-h urinary C-peptide excretion, fasting plasma C-peptide levels and plasma C-peptide levels after glucagon stimulation. Insulin antibodies were detected in 29% of the patients (8 out of 28). In all but one patient antibodies binding porcine and human insulin were detected. No relationship was found between the presence of antibodies binding human or porcine insulin at diagnosis and age. After 1 year 27 out of 28 patients presented insulin antibodies. No relationship was found between the presence of insulin antibodies before therapy and 1 year after therapy. Insulin antibodies prior to diagnosis showed no relationship with the urinary C-peptide excretion at diagnosis (with antibodies 67 +/- 27%, without antibodies 76 +/- 11%). However, after 1 year significantly lower urinary C-peptide excretions were found in patients with insulin antibodies prior to therapy (with antibodies, 17 +/- 7%, without antibodies, 31 +/- 5%, p less than 0.02). Peak plasma C-peptide levels after 1 year were possibly lower in patients with insulin antibodies before treatment (with antibodies 0.17 +/- 0.06 nmol/l, without antibodies 0.26 +/- 0.04 nmol/l, p less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide↗

PubMedDate not supplied

Glucose-induced insulin response is reduced and proinsulin response increased in healthy siblings of type 1 diabetic patients.

Glucose-stimulated insulin and proinsulin responses, and insulin sensitivity, were studied in 30 HLA identical, 38 HLA haplo-identical, and 25 HLA non-identical, healthy islet-cell-antibody negative siblings of Type 1 diabetic patients. The results were compared with 41 age- and sex-matched healthy subjects with no diabetes in the family. The proinsulin-corrected insulin response to an intravenous glucose infusion test was significantly lower among siblings when insulin sensitivity was taken into account (1.65 (inter-quartile range 1.20-2.64) vs 2.18 (1.65-3.28) nmol mmol-1 min, p = 0.04). Proinsulin values were consistently higher among siblings than among control subjects (peak values 50.0 vs 38.0 pmol l-1 (p = 0.004)). When proinsulin release was corrected for individual insulin sensitivity this difference remained. The results suggest disturbed islet B-cell function, unrelated to HLA identity or the presence of circulating islet cell antibodies.

Adolescent↗

PubMedDate not supplied

Creatinine height index and lean body mass in adult patients with insulin-dependent diabetes mellitus followed for 7 years from onset.

The 24-hour urinary creatinine excretion value can be used as an index of protein nutrition; the creatinine height index and lean body mass can be estimated from this value. On the basis of longitudinally measured 24-hour urinary creatinine excretions during the initial 7 years of type 1 diabetes in an incidence cohort of 147 adult patients, we studied creatinine height index and lean body mass and possible relationships to sequential measurements of glycated hemoglobin (HbA1c). The patients were divided into four groups according to their glycemic control during these 7 years: I, HbA1c < 7.4% (n = 37); II, HbA1c 7.4% to 8.2% (n = 37); III, HbA1c 8.3% to 8.9% (n = 38); IV, HbA1c > 8.9% (n = 35). One year after the onset of diabetes, height indices were as follows (% of normal values, median and quartiles): I, 104% (90 to 116); II, 101% (78 to 105); III, 121% (92 to 128); IV, 87% (78 to 109) ([IV] < [I to III]; p < .05). During the following 6 years no significant differences in height index were observed among the four groups of patients at any point in time. Slightly higher calculated lean body mass values were found in the most well-controlled patients, but otherwise no differences were found in lean body mass. It is concluded that, apart from the first year, indices of protein nutrition remain normal during the initial 7 years of type 1 diabetes, even in patients with poor glycemic control.

Adult↗

PubMedDate not supplied

Remission in IDDM: prospective study of basal C-peptide and insulin dose in 268 consecutive patients.

To elucidate beta-cell function, insulin requirement, and remission period in insulin-dependent diabetes mellitus (IDDM), a study was undertaken comprising 268 patients consecutively admitted to Steno Memorial Hospital with newly diagnosed IDDM. The patients were characterized by sex, age, and seasonal variation at onset of diabetes mellitus. During the first 36 mo of the disease, an evaluation was performed for basal C-peptide, HbA1c, and insulin dose per kilogram. Total remission was interpreted as complete discontinuation of insulin therapy for at least 1 wk while still metabolically well controlled, and partial remission was interpreted as an insulin need that was less than or equal to 50% of the insulin dose at discharge from the hospital. During the first 18 mo of the disease, 12.3% of the patients entered total remission (median 6 mo), and 18.3% of the patients entered partial remission (median 6 mo). Patients entering remission had significantly higher basal C-peptide levels than those who did not. Sex, age, and initial HbA1c levels did not influence the frequency of remission.

Adolescent↗

PubMedDate not supplied

Influence of smoking on insulin requirement and metbolic status in diabetes mellitus.

This study was performed in order to examine the influence of tobacco smoking on carbohydrate and lipid metabolism and microangiopathy in diabetic patients with normal serum creatinine. Among 163 adult insulin-treated patients 114 smoked daily (smokers). Compared with nonsmokers, smokers had on the average a 15--20% higher insulin requirement (P < 0.001) and serum triglyceride concentration (P < 0.05), increasing to a 30% rise in heavy smokers (P < 0.01). The degree of retinopathy was equal in the two groups, as was the average creatinine clearance [99 +/- 2 (mean +/- 1 SEM) versus 101 +/- 4 ml/min in smokers compared with nonsmokers]. Smokers and nonsmokers were comparable regarding sex ratio, age at diabetic onset, duration of diabetes, residual beta-cell function, fasting hyperglycemia, and glycosuria. Evidently, tobacco smoking represents a strain on both carbohydrate and lipid metabolism in insulin-treated diabetes mellitus.

Adult↗

PubMedDate not supplied

Insulin pharmacokinetics.

Where adjustments of diet, physical activity, and dosage of insulin are well known to diabetologists and diabetic patients, present-day knowledge of factors of importance to the pharmacokinetics of insulin is frequently ignored. The pharmacokinetics of insulin comprise the absorption process, the distribution including binding to circulating insulin antibodies, if present, and to insulin receptors, and its ultimate degradation and excretion. The distribution and metabolism of absorbed insulin follow that of endogenous insulin. The distribution and metabolism cannot be actively changed, except in the case of circulating insulin antibodies, which in rare cases also may cause insulin resistance. The use of insulin preparation of low immunogeneity will avoid or reduce this course of variation in action. The absorption process, the detailed mechanisms of which are still unknown, is influenced by many variables where some can be controlled, thereby reducing the intrapatient variability in insulin absorption, which may reach 35%, causing a corresponding metabolic lability. Besides the known differences in timing among different preparations, the size of dose, the injected volume, and the insulin concentration are determinants of absorption role. Fortuitous injection technique contributes to variance, as do changes in blood flow of the injected tissue. This may be induced by changes in ambient temperature, exercise of injected limb, or local massage. Regional differences are also due to differences in blood flow. Serum insulin peaks may peak up to 1 h after injection of soluble insulin into the thigh versus into the abdominal wall. Local degradation of insulin seems of less importance but may, in rare cases, be the cause of high insulin "requirements." Available evidence is reviewed and the importance of implementing the consequences in the daily care of the insulin-treated patient is emphasized.

Absorption↗

PubMedDate not supplied

Caspase-activation and induction of inducible nitric oxide-synthase during TNF alpha-triggered apoptosis.

Activation of the intracellular "death domain" (DD) of the 55kD-TNF alpha-receptor by TNF alpha initiates signal and effector cascades with pro- and anti-apoptotic function. Co-activation of the adjacent "NO-domain" is followed by induction of inducible nitric oxide-synthase (iNOS) and generation of nitric oxide radicals (NO.). Recently, we have shown NO.-generation to be essential for TNF alpha-induced apoptosis of various tumor cell lines. However, the impact of iNOS activation in relation to other promoters of apoptosis, such as the caspases, is still unclear. Caspase activation, iNOS induction and death rate were therefore investigated in TNF alpha-treated MCF-7 cells. Incubation with TNF alpha (+/- cycloheximide) led to activation of the caspase cascade and was followed by apoptosis. Simultaneously, TNF alpha stimulated induction of iNOS and generation of NO.. Caspase inhibitors DEVD-CHO, YVAD-cmk and YVAD-CHO effectively inhibited caspase activation and prevented apoptosis. Apoptotic cell death was decreased to a similar degree following inhibition of iNOS by L-nitro-arginine-methyl-ester (L-NAME). Cell death suppression by caspase inhibition did not result in reduced iNOS activity, as well as L-NAME-dependent prevention of apoptosis was not associated with caspase inactivation. Taken together, TNF alpha induces apoptosis in MCF-7 cells by initiating a two-sided effector pathway including iNOS-induction and activation of caspase 1- and 3-like proteases. Both mechanisms seem to be equally essential for the execution of the death program. The exact nature of their cooperation needs further clarification.

Adenocarcinoma↗

PubMedDate not supplied

Helicobacter pylori-induced hyperproliferation: relevance for gastric cancer development in connection with mutagenic factors.

AIMS: Current data on Helicobacter pylori induced regenerative hyperproliferation of the antral gastric mucosa and significance in cancer development are still under discussion and investigation. An improved method for evaluation of the regeneratory process in antral mucosa is introduced and compared with the conventional method used for determination of proliferating cells in perpendicular sections of the gastric mucosa. METHODS: Using a combination of immunohistochemistry and PAS-staining the expression of Ki-67 (MiB1)-proliferation associated antigen was analyzed in 50 Helicobacter pylori (Hp) positive and 35 negative biopsies of the gastric antrum. PAS-staining was performed to identify the proliferative zone of the antral gastric glands. The degree of inflammation was evaluated by grades on routinely H & E-stained slides. RESULTS: Proliferative activity is significantly increased in Hp-positive cases (p = 0.00095) compared to negative ones. By using the conventionally applied proliferation index, every nucleus has to be counted and the proliferation zone is identified by at least one positive stained nucleus. The method presented here seems to be easier because the proliferative zone is clearly identified by PAS staining of neutral glycoproteins characteristic for the proliferation zone of antral glands. The density of labeled nuclei is determined and is expressed as a proliferation factor. This factor gives more distinct values, is easier to evaluate and shows a better correlation with the helicobacter status and the degree of inflammation. These results are discussed in relation to the data from the literature and with a view to other relevant factors in the course of carcinogenesis, such as growth factors, mainly EGF, p53 mutation and role of apoptosis, genetic instability and local production of oxidants. CONCLUSION: Helicobacter pylori induces an increase of regenerative proliferation activity. Under these conditions the chance of mutation is increased and time for DNA repair reduced. This could be at least a part of multiple step carcinogenesis. The newly introduced combination of staining procedures (PAS/MiBI) allows a more differentiated evaluation of the proliferation zone and its widening. This method can be more easily handled in follow-up studies than the method using perpendicular sections because in this method heavy irregularities of gland pattern induced by accompanying inflammatory processes considerably hinder evaluation.

Cell Division↗

PubMedDate not supplied

Differential expression of apoptosis associated genes bax and bcl-2 in ovarian cancer.

The prognostic value of various molecular markers, which adequately account for the tumor biology and disease behaviour of ovarian cancer, is still unclear. Recent studies have focused on the role of genes regulating the balance between proliferation and cellular suicide, apoptosis. In the present study, tumor tissue from 215 patients with ovarian cancer was immunohistochemically analysed for Bax- and Bcl-2-expression. There was an association between Bcl-2-expression (30%) and factors of favourable prognosis. In contrast, Bax-expression (47%) was related to bad clinical outcome, especially in cases without concomitant Bcl-2-expression. In patients with Bcl-2-positive/Bax-negative tumors, overall survival was significantly longer (p = 0.0379) than in patients with Bcl-2- and Bax-negative tumors. Respectively, expression of Bax without Bcl-2-expression was correlated with bad clinical outcome (p = 0.033). The difference in overall survival was most striking (p = 0.0007) between patients with Bax-positive/Bcl-2-negative and Bcl-2-positive/Bax-negative tumors. This could also be demonstrated for the various subgroups of different tumor grade and stage. It may be speculated, that alteration of the Bax/Bcl-2-balance may influence the clinical course by deregulation of programmed cell death and altered sensitivity to chemotherapy.

Adenocarcinoma, Clear Cell↗

PubMedDate not supplied

Deregulated simultaneous expression of multiple glucose transporter isoforms in malignant cells and tissues.

To evaluate the molecular and functional characteristics of upregulated glucose uptake in malignant cells, the expression of four glucose transporter (Glut) isoforms as well as glucose transport were determined in benign and malignant cell lines and tissues. In vivo distribution of Glut proteins was examined by immunocytochemistry in 30 breast cancer samples. In comparison with benign controls upregulation of Glut 1 mRNA and Glut 3 mRNA was shown. Glut 2 mRNA could not be detected. Glut 4 mRNA was found in various malignant cell lines in contrast to the physiological restriction of Glut 4 to terminally differentiated muscle and fat cells. While Glut 3 protein was not detectable in non-neuronal tissues, the degree of overexpression of Glut 1 and 4 corresponded to the expression level of the respective mRNAs. 57% of the breast cancer tissues showed positivity for Glut 1, 43% for Glut 4. Functional integrity of Glut 4 was demonstrated by preserved insulin-responsiveness. In cell lines, glucose transport activity was positively correlated with proliferation rate. Enhanced translocation of Glut 4 to the plasma membrane in correlation with high Ki-67 positivity in tissues pointed to the same association in vivo. C-myc overexpression had no detectable influence on Glut expression. In conclusion, malignant cells demonstrate quantitative as well qualitative changes of Glut expression and activity. Alteration of differentiation-adapted transcription and expression of cell-specific Gluts may represent a part of the transformation process and contribute to tumor progression.

Adult↗

PubMedDate not supplied

Breast preserving surgery decision making.

Mammography, and in special cases MRT, allow the detection of DCIS and microcarcinomas. Breast preserving surgery needs intraoperative care for tumor free margins. Decision making under favourable and unfavourable conditions is discussed. Tumor grading is important with respect to locoregional recurrences. Improvements in breast cancer diagnosis are discussed in a separate paper in the same volume. The significance of c-erbB2 in pT1N0M0 stage has been determined in 472 cases. Within the c-erbB family, c-erbB2 has highest significance. p53 should also be evaluated with respect to tumor progress. In a few cases of malignant cystosarcoma phyllodes, p53 reaction was found in epithelial and mesenchymal cell systems. These results correspond to the results of Domagala et al (90) which show that vimentin positivity correlates with high proliferation, a high degree of malignancy and c-erbB2 positivity. Finally, the significance of angiogenesis with respect to the ineffective knot-formation for tumor cell transport and detachment of epithelia with apoptosis are discussed. The significance of proteolytic activity of cancer according to the results of Schmitt et al (89) is included in the discussion. Biochemical analysis seems to be much more effective for prediction of metastatic process as compared with immunohistochemical evaluations.

Breast Neoplasms↗