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Biomedical subjects

B Winkler

Publications and source records attributed to B Winkler.

At least 37 records · Page 2Linked to original sources
PubMed1997

Angiogenesis but not collateral growth is associated with ischemia after femoral artery occlusion.

It remains unclear whether capillary sprouting (angiogenesis) and in situ growth of muscular collateral arteries share the same or different molecular mechanisms. To study the role of ischemia in these two forms of vascular proliferation, we measured tissue flows and maximum collateral conductances in hindlimbs of 22 rabbits previously subjected to either acute, 7-day, 21-day, or no femoral artery occlusion. After 1 wk of femoral artery occlusion, corkscrew collaterals were observed radiographically in the thigh. These collaterals showed histochemical evidence for active proliferation of endothelial and smooth muscle cells. Maximum collateral conductance increased sixfold in the 1st wk. Perfusion deficits, however, were only observed in the distal adductor muscles (region of collateral reentry). In the lower leg, which suffered from a profound perfusion deficit, conductance increased in the absence of any visible collateral arteries but with evidence for capillary proliferation. This study therefore demonstrates that upon femoral artery occlusion angiogenesis occurs in regions of profound ischemia, whereas no direct correlation can be drawn between ischemia and collateral artery development.

Angiography↗
PubMed1997

Monocyte chemotactic protein-1 increases collateral and peripheral conductance after femoral artery occlusion.

Monocytes are activated during collateral artery growth in vivo, and monocyte chemotactic protein-1 (MCP-1) has been shown to be upregulated by shear stress in vitro. In order to investigate whether MCP-1 enhances collateral growth after femoral artery occlusion, 12 rabbits were randomly assigned to receive either MCP-1, PBS, or no local infusion via osmotic minipump. Seven days after occlusion, isolated hindlimbs were perfused with autologous blood at different pressures, measuring flows at maximal vasodilation via flow probe and radioactive microspheres, as well as peripheral pressures. This allowed the calculation of collateral (thigh) and peripheral (lower limb) conductances from pressure-flow tracings (slope of the curve). Collateral growth on postmortem angiograms was restricted to the thigh and was markedly enhanced with MCP-1 treatment. Both collateral and peripheral conductances were significantly elevated in animals with MCP-1 treatment compared with the control group, reaching values of nonoccluded hindlimbs after only 1 week of occlusion (collateral conductance, 70.6 +/- 19.23 versus 25.1 +/- 2.59 mL/min per 100 mm Hg; P < .01; peripheral conductance, 119.3 +/- 22.37 versus 45.4 +/- 6.80 mL/min per 100 mm Hg; P < .05). These results suggest that activation of monocytes plays an important role in collateral growth as well as in capillary sprouting.

Angiography↗
PubMed1997

[Angiofollicular lymph node hyperplasia (Castelman's disease) in an adult woman].

Angiofollicular lymph node hyperplasia Castleman's disease) is a rare disorder of unclear etiology and wide spectrum of systemic symptoms. This report describes a case of this disorder of hyalinovascular type in 45-years old woman. The lesions were localized in axillary lymph nodes. The disease was curable by surgical excision.

Castleman Disease↗
PubMed1997

Potassium and thallium uptake in dog myocardium.

UNLABELLED: We sought to ascertain the rates and mechanisms of uptake of markers for regional myocardial blood flows. METHODS: The rates of exchange of potassium and thallium across capillary walls and cell membranes in isolated blood-perfused dog hearts were estimated from multiple indicator dilution curves recorded for 131I-albumin, 42K and 201Tl from the coronary sinus outflow following injection into arterial inflow. Analysis involved fitting the observed dilution curves with a model composed of a capillary-interstitial fluid-cell exchange region and nonexchanging larger vessels. RESULTS: Capillary permeability surface products (PSc) for potassium and thallium were similar, 0.82 +/- 0.33 (mean +/- s.d., n = 19) and 0.87 +/- 0.32 ml min-1 g-1 (n = 24) with a ratio for simultaneous pairs of 1.02 +/- 0.27 (n = 19). For the myocardial cells, PSpc averaged 3.7 +/- 3.1 ml min-1 g-1 (n = 19) for K+ and 9.5 +/- 3.9 (n = 24) for Tl+; the ratio of potassium to thallium averaged 0.40 +/- 0.19 (n = 18), thereby omitting a single high value for potassium. This high cellular influx for thallium is interpreted as due to its passage through ionic channels for both Na+ and K+. CONCLUSION: The high permeabilities and large volumes of distribution make thallium and potassium among the best ionic deposition markers for regional flow. Their utility for this purpose is compromised by significant capillary barrier limitation retarding uptake; so regional flow is underestimated modestly in high-flow regions particularly.

Animals↗
PubMed1994

Antiphospholipid syndrome associated with immunotherapy for patients with melanoma.

BACKGROUND: Immunotherapy for patients with cancer is associated with severe side effects, including the possible induction of autoantibodies. The latter was proven for antithyroid microsomal and antithyroglobulin antibodies. METHODS: This study was designed to evaluate antiphospholipid antibodies (APA) in 30 patients receiving three different forms of immunotherapy for disseminated melanoma using interleukin-2 (IL-2), alpha-interferon (alpha-interferon) or the combination of both. RESULTS: APA were detected in none of 18 patients treated with IL-2 alone, 2 of 4 (50%) treated with alpha-interferon alone, and 3 of 8 (37.5%) treated with the combination of both. In the last group, increased concentrations of APA were observed, while the patients were still receiving alpha-interferon alone. APA levels were not detected in any of 10 patients with melanoma who were not treated with alpha-interferon or IL-2. In patients with increased APA, five of five (100%) had a prolongation of the partial thromboplastin time and 4 or five (80%) had deep venous thrombosis, which in one patient was followed by pulmonary embolism. CONCLUSIONS: The high incidence of therapy-induced elevated APA concentrations suggests that these should be carefully monitored in all patients receiving immunotherapy with alpha-interferon.

Adult↗
PubMed1994

Development, application and comparison of an enzyme immunoassay and a high-performance liquid chromatography method for the determination of the aromatase inhibitor CGS 20,267 in biological fluids.

CGS 20,267 is a new potent and selective, nonsteroidal, oral aromatase inhibitor. For its determination in human plasma and urine, an enzyme immunoassay (EIA) and an HPLC method were developed. The EIA showed good precision and accuracy (intra- and interassay variation between 3.0 and 17.7%, recoveries between 81 and 106%) and a quantitation limit of 0.7 nmol/L. A strong cross reactivity of the antibodies with the hydroxy metabolite of CGS 20,267 (CGP 44,645) was observed. The HPLC method showed a quantitation limit in plasma of 28 and 34 nmol/L for CGS 20,267 and CGP 44,645, respectively. For urine, concentrations down to 180 nmol/L (CGS 20,267) and 210 nmol/L (CGP 44,645) could be measured. A cross check between EIA and HPLC on plasma samples from healthy male volunteers or breast cancer patients treated orally with CGS 20,267 revealed an excellent correlation (slope = 0.934, intercept = 26, r = 0.991). However, the EIA measurements of urine samples yielded 3-25 times higher concentrations than those obtained by HPLC. Further, HPLC analysis revealed the presence of CGS 20,267 and cross-reacting metabolites in urine but not in plasma. Therefore, the EIA can only be used for the determination of CGS 20,267 in plasma samples.

Animals↗
PubMed1992

The metabolic effects of oxytocin are mediated by a uterine type of receptor and are inhibited by oxytocin antagonist and by arginine vasopressin in the dog.

Infusion of oxytocin (OT) into normal dogs, in doses which produced plasma levels of OT in the physiological range, has been shown to increase plasma levels of glucose, insulin and glucagon and increase rates of glucose production and uptake. This study sought to determine whether there was a correlation between these metabolic effects and the oxytocic potency of four less potent oxytocic analogues when infused into normal dogs. The rank order of oxytocic potency of all 4 correlated well with the rise in plasma glucose levels, and in 3 of the 4 with the rise in plasma insulin levels. An antagonist of the oxytocic effect of OT suppressed the usual OT-induced rise in plasma glucose, insulin and glucagon as well as the increased glucose production and uptake. Arginine vasopressin (AVP) infusion, which by itself did not produce any metabolic effects, blocked completely the effects of OT infusion to raise plasma glucose and insulin levels and increase glucose production and uptake. The data suggest that the metabolic effects of OT in the dog are mediated by OT receptors that are similar to those producing the oxytocic effects. Whether the inhibition by AVP of the metabolic and hormonal effects of OT occurs at the receptor or post receptor level or via other mechanisms remains to be determined.

Animals↗
PubMed1992

Role of insulin and glucagon in oxytocin effects on glucose metabolism.

Oxytocin (OT) infusion in normal dogs increases plasma insulin and glucagon levels and increases rates of glucose production and uptake. The purpose of this study was to determine whether the effects of OT on glucose metabolism were direct or indirect. The studies were carried out in normal, unanesthetized dogs in which OT infusion was superimposed on infusion of either somatostatin, which suppresses insulin and glucagon secretion, or clonidine, which suppresses insulin secretion only. Infusion of 0.2 microgram/kg/min of somatostatin suppressed basal levels of plasma insulin and glucagon and inhibited the OT-induced rise of these hormones by about 60-80% of that seen with OT alone. The rates of glucose production and uptake by tissues, measured with [6-3H] glucose, were significantly lower than those seen with OT alone, and the rise in glucose clearance was completely inhibited. Clonidine (30 micrograms/kg, sc), given along with an insulin infusion to replace basal levels of insulin, completely prevented the OT-induced rise in plasma insulin and markedly reduced the glucose uptake seen with OT alone, but did not reduce the usual increase in plasma glucose and glucagon levels or glucose production. To determine whether the OT-induced rise in plasma insulin was in response to the concomitant increase in plasma glucose, similar plasma glucose levels were established in normal dogs by a continuous infusion of glucose and an OT infusion was superimposed. OT did not raise plasma glucose levels further, but plasma insulin levels were increased, indicating that OT can stimulate insulin secretion independently of the plasma glucose changes. Studies by others have shown that the addition of OT to pancreatic islets or intact pancreas can stimulate insulin and glucagon secretion, indicating a direct effect. Our studies agree with that and suggest that in vivo, OT raises plasma insulin levels, at least in part, through a direct action on the pancreas. These studies also show that OT increases glucose production by increasing glucagon secretion and, in addition, a direct effect of OT on glucose production is likely. The OT-induced increase in glucose uptake is mediated largely by increased insulin secretion.

Analysis of Variance↗
PubMed1991

Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues.

The role of human papillomavirus (HPV) proteins in the pathogenesis of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer is poorly understood. To characterize E4 protein expression in 49 paraffin-embedded cervical biopsies representing different histopathologic grades of disease, antibodies were elicited to a synthetic peptide corresponding to amino acids 20-34 of a protein predicted to be encoded by the HPV 16 E4 open reading frame. The E4 protein was detected throughout the spectrum of CIN, from CIN1 to CIN3. Expression was localized to the cell nucleus, primarily in the superficial layers of the squamous cervical epithelium. Ultrastructural studies showed that the E4 protein was organized into compact, intranuclear arrays 25-35 nm in diameter. E4 protein expression was also demonstrated in some histologically normal tissues containing HPV 16 DNA, but not in any of five cervical cancers containing HPV 16 DNA. These results suggest that E4 protein expression may precede development of light microscopic tissue abnormalities, that it may continue through the spectrum of CIN, and that expression of this protein may be reduced or terminated in invasive cancer. The function of this protein remains unknown, but its nuclear localization may be consistent with a role in viral maturation.

Amino Acid Sequence↗
PubMed1990

The dorsal antiglide plate in the treatment of Danis-Weber type-B fractures of the distal fibula.

The results of 93 of 107 consecutive antiglide plate internal fixations of Danis-Weber Type-B fractures of the distal fibula are reported with a follow-up period of just over one year. Using the ankle evaluation scale of Weber, 66.7% excellent, 27.9% good, and only 5.4% poor results were found. The method of dorsal antiglide plate fixation is possible in most of the frequent Type-B ankle fractures. Stabilization is better with the antiglide plate, especially in older patients with osteoporotic bone. Because of these advantages and the biomechanically sound technique, the antiglide plate is recommended for stabilization of the Danis-Weber Type-B fracture of the distal fibula.

Ankle Injuries↗
PubMed1989

Differences in biologic maturation, sexual behavior, and sexually transmitted disease between adolescents with and without cervical intraepithelial neoplasia.

Because several cofactors may influence the development of cervical intraepithelial neoplasia (CIN) in young women, we compared differences in behaviors (sexual activity, contraception, and cigarette use), sexually transmitted disease (STD) infection rates (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and herpes simplex virus), and cervical maturation (age of menarche and percentage of cervical ectopy) in groups of sexually active female adolescents with and without CIN. Those with CIN were compared with three non-CIN groups: (1) teenagers who were referred to a teen colposcopy clinic but had no evidence of CIN (high-risk group), (2) teenagers seen at a gynecology clinic without STD symptoms (asymptomatic group), and (3) teenagers seen at the gynecology clinic with STD symptoms (symptomatic group). The percentage of cervical ectopy was measured by colpophotography. Subjects with CIN had more lifetime sexual partners than the asymptomatic group (p less than 0.001) and were more likely to smoke cigarettes than either gynecology clinic group (p less than 0.01). No differences in behaviors existed between the CIN and high-risk groups. The mean age of menarche in those with CIN was 1 year older than all three non-CIN groups (p less than 0.05), and those with CIN had a greater area of ectopy than those without CIN (p less than 0.02). Those with CIN were more likely to have a past or present history of C. trachomatis infection than the two gynecology clinic groups; no difference was found between the CIN and high-risk groups. We conclude that cofactors such as smoking, sexual promiscuity, and C. trachomatis infection may influence cervical vulnerability. However, cervical biologic immaturity is an important risk factor for development of CIN in adolescent girls.

Adolescent↗
PubMed1989

Endometrial polyps in postmenopausal patients receiving tamoxifen.

The histologic features of an endometrial polyp include irregular, often dilated glands, thick-walled blood vessels, and a fibrotic stroma. Such polyps may be responsive to some chemotherapeutic drugs that can exert hormonal effects. We report on endometrial polyps detected in three postmenopausal patients who were receiving tamoxifen for treatment of metastatic breast carcinoma. The clinical presentation in all cases was vaginal bleeding and all had documented uterine enlargement suggestive of an intrauterine malignancy. The polyps were large, measuring up to 9 cm in largest diameter. On histologic examination each polyp had extensive cystic glandular hyperplasia. In one case foci of atypical epithelial proliferation and predecidualization were noted. The atypical proliferation suggested a borderline neoplastic process and was strongly positive for carcinoembryonic antigen. These findings underscore the marked proliferative changes that can be induced in endometrial polyps in postmenopausal women receiving hormonally active chemotherapeutic agents.

Aged↗
PubMed1987

Influence of collateral blood flow and of variations in MVO2 on tissue-ATP content in ischemic and infarcted myocardium.

The left anterior descending coronary artery was occluded for 22.5, 45, 90, 180, and 360 mins in anesthesized open-chest dogs and pigs and thereafter reperfused for 30 min. Myocardial oxygen consumption was varied in dogs by cholinergic stimulation (bradycardia) and by cutting of the right and left vagus nerve (tachycardia). Regional myocardial blood flow was measured with radioactive tracer microspheres at the end of the occlusion period and 5 and 30 min after reflow. Tissue content of adenine nucleotides and of phosphocreatine were determined in the subendo- and subepicardium of transmural biopsies at the end of reflow. Infarct size was determined with nitrobluetetrazolium and compared with risk region size. Porcine hearts developed infarcts sooner. Those canines with a high MVO2 due to tachycardia had larger infarcts than those with bradycardia and resembled infarct development in the pig. The evolution of infarcts with time depended strongly on collateral flow which was significantly higher in canine hearts. Higher collateral flow and lower MVO2 in one group of canine hearts also resulted in better preserved tissue ATP. The fall in tissue ATP with time after coronary occlusion was compared with the O2-supply via collateral flow during occlusion. Assuming that the oxygen entering ischemic myocardium was used for ADP phosphorylation, we could estimate the degree of ATP-"overspending". Overspending was highest in low-flow ischemia and it correlated well with the speed of infarction. The ATP-data are best explained by the phosphocreatine energy shuttle model and by assuming slow access of cytosolic ATP to the ATP-splitting sites at the myofibrils. In conclusion, we postulate that both collateral flow as well as myocardial oxygen consumption before and during occlusion determine infarct size.

Adenine Nucleotides↗
PubMed1987

Fine-needle aspiration biopsy in the management of cervical carcinoma following primary therapy.

Thirty-five fine-needle aspiration biopsies (FNAB) in 30 patients who had previously received primary therapy for cervical carcinoma are reported. There were 22 positive FNABs, and in 11 cases the positive FNAB definitely changed the patient's planned therapy. There were no complications due to FNAB in these 30 patients. FNAB has an important role in follow-up and management of patients with cervical carcinoma.

Adenocarcinoma↗