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Biomedical subjects

H Heinzl

Publications and source records attributed to H Heinzl.

At least 37 records · Page 2Linked to original sources

Drug resistance factors in acute myeloid leukemia: a comparative analysis.

To compare the clinical relevance of drug resistance factors in de novo acute myeloid leukemia (AML), we determined their relationship to both response to induction chemotherapy and survival of the patients in univariate as well as multivariate analyses. The drug resistance factors immunocytochemically studied in 111 patients at the time of diagnosis included the lung resistance protein (LRP), P-glycoprotein (P-gp), multidrug resistance protein (MRP1) and bcl-2. In the univariate analyses, age (P = 0.005), karyotype (P = 0.03), LRP (P = 0.003), P-gp (P = 0.02) and bcl-2 (P = 0.03) predicted for response to induction chemotherapy, whereas MRP1 had no predictive value. Age (P = 0.05), karyotype (P = 0.05) and LRP (P = 0.03) retained their predictive value in the multivariate logistic regression analyses. With regard to overall survival, age (P = 0. 008), karyotype (P = 0.006), LRP (P = 0.001) and P-gp (P = 0.01) were of prognostic value in the univariate Cox regression analyses but only age (P = 0.01), karyotype (P = 0.02) and LRP (P = 0.01) retained their prognostic significance in the multivariate analyses. A risk score based on the number of independent prognostic factors allowed division of patients into four groups with different outcome. In these groups, the complete remission rates were 93%, 75%, 47% and 33%, respectively, and median overall survival was 2.4, 1.2, 0.6 and 0.2 years, respectively. Thus, several drug resistance factors did predict outcome in the univariate analyses but LRP was the only drug resistance factor with independent predictive and prognostic significance. The proposed risk score might be useful for risk-adapted treatment in the future. Leukemia (2000) 14, 68-76.

Acute Disease↗

Cardiac autonomic function in patients suffering from primary focal hyperhidrosis.

Cardiac autonomic function in patients (n = 63) with primary focal hyperhidrosis and healthy controls (n = 28) was investigated by short-term frequency domain power spectral analysis of heart rate variability. The power of the very-low-frequency band (0.01-0.05 Hz) was significantly lower in patients with axillary hyperhidrosis than in controls. No differences between groups could be observed at investigation of the low-frequency band (0.05-0.15 Hz), which was a surprising finding because this band represents also sympathetic cardiac innervation. At the high-frequency band (0.15-0.5 Hz), which represents parasympathetic cardiac innervation, an interaction of type and position influencing spectral power was detected. Our highly interesting findings indicate that primary focal hyperhidrosis is based on a much more complex autonomic dysfunction than generalised sympathetic overactivity and seems to involve the parasympathetic nervous system as well.

Adult↗

Clinical relevance of the lung resistance protein in diffuse large B-cell lymphomas.

Drug resistance of non-Hodgkin's lymphomas may involve mechanisms of the multidrug resistance phenotype including the lung resistance protein (LRP) and the multidrug resistance protein (MRP1). To determine the clinical relevance of these multidrug resistance factors in previously untreated diffuse large B-cell lymphomas (n = 48), we studied LRP and MRP1 expression in lymphoma cells and their impact on clinical outcome. LRP and MRP1 expression were immunohistochemically assessed by means of the monoclonal antibodies LRP-56 and MRPr1, respectively. LRP was positive in 23% and MRP1 in 44% of the samples. LRP expression was associated with higher tumor stage (P = 0.03), elevated serum lactate dehydrogenase levels (P = 0.01), and the International Prognostic Index (P = 0.0001). LRP-positive patients had a lower complete response rate to polychemotherapy than LRP-negative patients (18 versus 65%; P = 0.006). Patients with LRP expression had a shorter overall survival than those without LRP expression (median of 0.9 years versus median not reached; P = 0.001). MRP1 expression was independent of clinical and laboratory parameters and had no impact on the outcome of chemotherapy or survival of the patients. These data suggest that LRP expression but not MRP1 expression is an important mechanism of drug resistance associated with worse clinical outcome in previously untreated diffuse large B-cell lymphomas. Thus, the reversal of LRP-mediated drug resistance may improve clinical outcome in diffuse large B-cell lymphoma in the future.

ATP-Binding Cassette Transporters↗

CA 125 regression after two completed cycles of chemotherapy: lack of prediction for long-term survival in patients with advanced ovarian cancer.

The prognostic influence of CA 125 regression between the time point before surgery and after two completed courses of chemotherapy was studied in 210 patients with advanced ovarian cancer, and was compared to other well established prognostic factors. CA 125 blood samples were collected preoperatively (CA 125 pre) and 3 months after surgery (CA 125 3 mo) (at the beginning of the 3rd cycle of chemotherapy). The parameter CA 125 regression defined as log10 (CA 125 3 mo/CA 125 pre) was used for statistical analysis. In a survival analysis using a Cox proportional hazards model, CA 125 regression (P = 0.0001), residual tumour (P = 0.0001), age (P = 0.0095) and grading (P = 0.044) were independent variables, whereas stage of disease, histology, ascites and type of surgery failed to retain significance. Using log10 (CA 125 3 mo/CA 125 pre) as simple covariate in a Cox model showed a hazard ratio of 1.70 (95% confidence interval 1.32-2.19, P = 0.0001). However, a detailed analysis of the interaction of time with the prognostic factor CA 125 regression on survival revealed a strong time-dependent effect with a hazard ratio of more than 6 immediately after two courses of chemotherapy, whereas within approximately 1 year the hazard ratio for the surviving patients dropped quickly to the neutral level of 1. In summary, CA 125 regression is an independent prognostic factor for survival of women with advanced ovarian cancer and allows an identification of a high-risk population among patients with advanced ovarian cancer. However, the discriminating power of serial CA 125 for long-term survival seems to be temporary and prediction of individual patients outcome is far less precise.

Adult↗

Induction of complete wound healing in recalcitrant ulcers by low-intensity laser irradiation depends on ulcer cause and size.

Chronic skin ulcers still represent a therapeutic challenge in dermatology. Among the various non-invasive treatment modalities used for the improvement of impaired wound healing, low-intensity laser irradiations are gaining an increasing body of interest. We used low-intensity laser irradiations delivered by a 30 mW helium-neon laser at an energy density of 30 J/cm2 three times weekly for the induction of wound healing in ulcers of diverse causes. Twenty patients with the same number of ulcers, which had previously been treated by conventional wound care for a median period of 34 weeks (range: 3-120 weeks) without any significant evidence of healing, were included in the study. Concerning the underlying disorders, patients were divided into four groups: diabetes, arterial insufficiency, radio damage and autoimmune vasculitis. In all ulcers, complete epithelization could be induced by laser therapy. No amputation or any other surgical intervention was necessary and no adverse effects of any kind were noted during low-intensity laser treatment. Regarding the different diagnoses, a statistically significant difference was noted (P = 0.008): ulcers due to radio damage healed significantly faster than those caused by diabetes (6 weeks [range: 3-10 weeks] vs. 16 weeks [range: 9-45 weeks], P = 0.005). Wound healing in autoimmune vasculitis (24 weeks [range: 20-35 weeks]) required longer than in radiodermitis, although the difference was not significant. In addition to the diagnosis, wound size was found to be an important factor influencing the duration of wound closure (P = 0.028), whereas duration of previous conventional treatment (P = 0.24) and depth (P = 0.14) showed no effect. Our results indicate that low-intensity laser irradiation could be a valuable non-invasive tool for the induction of wound healing in recalcitrant ulcers, and that healing time is correlated with the ulcer cause and size.

Adult↗

Local and systemic control after ablative and limb sparing surgery in patients with osteosarcoma.

Limb salvage surgery in patients with osteosarcoma is reported to cause a higher rate of local recurrences with a poorer chance of survival. It was the aim of the study to analyze differences between ablative and limb sparing surgery in patients with osteosarcoma who are treated with chemotherapy with respect to local and systemic tumor control and to determine independent prognostic factors. One hundred thirty consecutive patients younger than the age of 21 years who were operated on at the authors' institution for osteosarcoma of the extremities were reviewed. Histologic evaluations of surgical margins according to Enneking and coworkers revealed mostly wide (n = 109) and radical (n = 10) resection margins. The 5-year disease free survival rate was 60% for those patients treated by amputation and 71% for those treated by limb salvage. The overall local recurrence rate was 2.3%; 4.3% for ablation but only 1.2% for limb sparing surgeries. Multivariate analysis showed an independent effect of tumor volume, response to chemotherapy, and as expected, metastases at the time of diagnosis on overall survival. These data indicate that in patients where wide or radical tumor resection can be achieved, no difference in the outcome between ablative and limb sparing surgery occurred in local and systemic tumor control.

Adolescent↗

[Cytokeratin tumor markers in ovarian carcinoma: tissue polypeptide specific antigen (TPS) and M3/M21].

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker M3/M21 as a screening, prognostic, and monitoring marker for ovarian cancer and as a predictive marker in patients with adnexal masses. In order to determine the specificity of the M3/M21 test we investigated M3/M21 serum levels in several benign conditions. The cytokeratin tumor markers M3/M21 and Tissue Polypeptide Specific Antigen (TPS) were also investigated in the follow-up of ovarian cancer patients. We evaluated M3/M21 serum levels in 75 patients suffering from ovarian cancer FIGO stages Ia to III, using a prototype immunoradiometric assay (IRMA). Sera of patients with benign cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10, and 20 cases, respectively. Furthermore, we analyzed TPS serum levels by means of IRMA during the follow-up of 40 patients suffering from ovarian cancer. With a sensitivity of 57% and a specificity of 95% M3/M21 was not suitable as a screening marker for ovarian cancer. Although M3/M21 was able to discriminate between ovarian cancer and benign adnexal tumors (univariate logistic regression, p = 0.0003), M3/M21 did not provide additional information (in addition to CA 125) (multivariate logistic regression, p = 0.2). M3/M21 serum levels were elevated in several benign conditions such as liver cirrhosis and inflammatory bowel disease. In ovarian cancer patients elevated M3/M21 serum levels prior to therapy were associated with a poor overall and disease-free survival (log-rank test, p = 0.03, and log-rank test, p = 0.01, respectively). In patients with recurrent ovarian cancer M3/M21 and TPS showed median lead-time effects of 3.2 and 3.9 months, respectively. M3/M21, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor. M3/M21 and TPS are valuable tumor markers in the follow-up of ovarian cancer patients.

Adult↗

M3/M21 serum levels in women with adnexal masses and inflammatory diseases.

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin tumor marker M3/M21 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic factor in women with ovarian cancer. To determine the specificity of the M3/M21 test, we investigated M3/M21 serum levels in several benign conditions. This retrospective study comprises 37 patients with ovarian cancer FIGO stages Ia to III. Sera of patients with benign cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases, respectively. With a sensitivity of 57% and a specificity of 95%, M3/M21 is not suitable as a screening marker for ovarian cancer. Although M3/M21 is able to discriminate between ovarian cancer and benign adnexal tumors (univariate logistic regression, p = 0.0003), M3/M21 does not provide information additional to CA 125. M3/M21 serum levels are elevated in several benign conditions such as liver cirrhosis and inflammatory bowel disease. In ovarian cancer patients, elevated M3/M21 serum levels prior to therapy were associated with poor overall and disease-free survival (log-rank test, p = 0.03; log-rank test, p = 0.01, respectively). M3/M21, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.

Adenocarcinoma↗

Influence of acupuncture on maternal serum levels of interleukin-8, prostaglandin F2alpha, and beta-endorphin: a matched pair study.

OBJECTIVE: To measure the serum levels of interleukin (IL)-8, prostaglandin (PG) F2alpha, and beta-endorphin in parturients with acupuncture treatment and in controls to clarify the effect of acupuncture and duration of labor on the serum levels of substances active in cervical ripening and dilatation. METHODS: A matched pair study was performed involving 80 women with and without prenatal acupuncture treatment, matched for age and parity. Serum levels of IL-8, PGF2alpha, and beta-endorphin were measured in serum samples taken after delivery by use of enzyme-linked immunosorbent assay, enzyme immunoassay, and immunoradiometric assay, respectively. RESULTS: The mean difference in total duration of labor between matched pairs with and without acupuncture was -136.5 minutes (95% confidence interval [CI] 191.1 minutes, -81.9 minutes; paired t test, P < .001). The mean difference of the duration of the first and second stages of labor between matched pairs with and without acupuncture was -138.8 minutes (95% CI 188.6, -89.0 minutes; paired t test, P < .001) and 2.3 minutes (95% CI 15.5, 20.1 minutes; paired t test, P = .8), respectively. The geometric means of ratios of IL-8, PGF2alpha, and beta-endorphin between matched pairs in women with and without acupuncture showed no statistically significant differences. Serum levels of IL-8, PGF2alpha, and beta-endorphin were not significantly correlated with the duration of the first and second stages of labor. CONCLUSION: Prenatal acupuncture treatment significantly reduces the duration of labor and may be a valuable tool in prenatal preparation. Serum levels of IL-8, PGF2alpha, and beta-endorphin are not significantly influenced by acupuncture and are therefore not likely to mediate acupuncture-related effects during labor.

Acupuncture Analgesia↗

Influence of delayed staging laparotomy after laparoscopic removal of ovarian masses later found malignant.

OBJECTIVE: To determine whether delayed laparotomy after attempted laparoscopic excision of an ovarian mass later found to be malignant has an impact on the stage of disease. METHODS: A questionnaire regarding laparoscopic management of ovarian masses later found to be malignant was mailed to all gynecologic departments in Austria. Of the 70 cases reported, laparotomy was performed after laparoscopy in 48 cases. In 24 of these cases, laparotomy was performed within 17 days of laparoscopy, whereas 24 cases involved a delay of more than 17 days. Twenty-two patients in whom laparotomy was performed immediately after laparoscopy were used as controls. RESULTS: In patients with borderline tumors who underwent laparotomy more than 17 days after laparoscopy, the odds ratio (OR) for International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IV disease was 5.3 (95% confidence interval [CI] 0.40, infinity), compared with patients undergoing immediate laparotomy (multivariate analysis). Patients with invasive ovarian cancer who underwent laparotomy more than 17 days after laparoscopy had an OR of 9.2 (CI 0.92, 481) for stage IIB-IV disease compared with patients undergoing immediate laparotomy (multivariate analysis). In patients with borderline tumors, multivariate analysis showed that the timing of laparotomy is an independent prognostic factor for the stage of disease. In invasive ovarian cancer, none of the factors evaluated by multivariate analysis was found to be an independent prognostic factor for the distribution of disease stage. A delay between laparoscopy and laparotomy may affect adversely the distribution of disease stage. CONCLUSION: The timing of subsequent laparotomy was found to be a factor predictive of the distribution of disease stage.

Adolescent↗

Value of urethral pressure profilometry in the female incontinent patient: a prospective trial with an 8-channel urethral catheter.

OBJECTIVES: To measure the pressure profiles at different positions of the urethral circumference simultaneously. METHODS: Twenty-two women with symptoms of genuine stress incontinence underwent urogynecologic assessment and multichannel urethral pressure profilometry (UPP) at rest with a specially designed 8-channel urethral catheter with radial openings. RESULTS: The distribution pattern of maximum urethral closure pressure (MUCP) and functional urethral length (FUL) values were significantly different (P=0.004 and P=0.0004, respectively). Most of the highest MUCP values per patient were found between channels 2 and 4 (P=0.015); most of the greatest FUL values per patient were found between channels 3 and 4 (P=0.15). CONCLUSIONS: The data of our study substantiate asymmetric radial pressure distribution within the urethra and underline the necessity of cautious interpretation of results of conventional single-channel UPP, which might vary because of transducer orientation.

Female↗

Improved laparoscopic operating techniques using a digital enhancement video system.

We conducted a prospective, randomized trial in a piglet model to assess the advantages of a digital enhancement video system during difficult endoscopic procedures. Laparoscopic pelvic lymphadenectomy was performed with either conventional two-dimensional or digitally enhanced videoendoscopy. With equal amounts of extirpated lymph nodes, the operations performed with digitally enhanced videoendoscopy were significantly shorter (left lymphadenectomy p = 0.0001, right lymphadenectomy p = 0.001), had less blood loss and fewer false movements, and were associated with no complications, compared with those performed with a two-dimensional videosystem. Thus the accuracy of difficult laparoscopic techniques can be improved by three-dimensional visual perception.

Animals↗

CYFRA 21-1 serum levels in women with adnexal masses and inflammatory diseases.

The aim of the present study was to evaluate the clinical usefulness of the cytokeratin marker CYFRA 21-1 as a screening marker for ovarian cancer, as a predictive marker in patients with adnexal masses and as a prognostic marker in women suffering from ovarian cancer. In order to determine the specificity of the CYFRA 21-1 test, we have investigated CYFRA 21-1 serum levels in several benign conditions. This retrospective study comprises 37 patients suffering from ovarian cancer FIGO stages Ia-III. Sera from patients with benign ovarian cysts, endometriosis, pelvic inflammatory disease, inflammatory bowel disease and liver cirrhosis were evaluated in 90, 10, 38, 10 and 20 cases respectively. With a sensitivity of 41% and a specificity of 95%, CYFRA 21-1 was not suitable as a screening marker for ovarian cancer. Although CYFRA 21-1 was able to discriminate between ovarian cancer and benign adnexal tumours (univariate regression model, P = 0.0001), CYFRA 21-1 did not reveal additional information to CA 125 in a multivariate regression analysis (P = 0.06). CYFRA 21-1 serum levels were elevated in benign conditions such as liver cirrhosis, but not in endometriosis and inflammatory diseases. In ovarian cancer patients, elevated CYFRA 21-1 serum levels before therapy were associated with a poor overall and disease-free survival (log-rank test, P = 0.02 and log-rank test, P = 0.005 respectively). CYFRA 21-1, while obviously not suitable for screening or differential diagnosis of adnexal masses, could be useful as an additional prognostic factor in ovarian cancer patients.

Adnexal Diseases↗

Localization of matrix metalloproteinase-2 in uterine endometrium and ectopic implants.

We performed an immunohistochemical study on paraffin-embedded tissues to evaluate the invasion pattern of endometriotic implants by determination of matrix metalloproteinase (gelatinase A) expression. Endometriotic tissues (n=32) and uterine endometria (n=18) of patients with endometriosis and uterine endometria of normal-menstruating women without endometriosis (n=11) were examined. Endometriotic tissues showed statistically significantly stronger staining compared with uterine endometria. However, we did not find differences in staining between uterine endometrium of women with endometriosis and normal controls. Compared to uterine endometrium, ectopic endometrium has a significantly higher capacity to produce the latent forms (72 kD) of gelatinase A. This leads to the conclusion that endometriotic implants express the protease enabling the invasion of surrounding tissue.

Endometriosis↗

Carbocyanine postmortem neuronal tracing. Influence of different parameters on tracing distance and combination with immunocytochemistry.

Carbocyanines (DiI, DiA, DiO) are able to travel along membranes by diffusion and therefore have been used as postmortem neuronal tracers in aldehyde-fixed tissues. Surprisingly, detailed data on the influence of different parameters on tracing distances are still missing. This study was carried out to optimize tracing procedures and to reveal the validity of the combination of postmortem tracing with immunocytochemistry. Carbocyanine crystals were applied to the cervical spinal cord, sciatic nerves, and brachial plexuses of humans and guinea pigs. Incubation in the dark at 37C for 12-15 weeks proved optimal to achieve longest tracing distances (28.9 +/- 2.2 mm) in human and animal tissues. Longer incubation times and incubation temperatures higher than 37C did not result in longer tracing distances. No differences were evident between adult and newborn animals and between central and peripheral nervous system. The diffusion coefficient for DiI was calculated to be 2.5 x 10(-7) cm2 sec-1. After application of DiI to nerves of guinea pig extraocular muscles, DiI-positive afferent perikarya were observed in the anteromedial part of the trigeminal ganglion. These perikarya were identified by calcitonin gene-related peptide immunoreactivity (CGRP-IR). The percentage of CGRP-IR neurons after tracing was concordant with the percentage of CGRP-IR in trigeminal ganglia exclusively processed for CGRP-IR without previous postmortem tracing. These results demonstrate carbocyanines to be specific tracers for exact neuronal mapping studies. (J Histochem Cytochem 46:901-910, 1998)

Aged↗

Endothelial eicosanoid metabolism and signal transduction during exposure to oxygen radicals injury.

Several physiological agonists that induce elevation of cytosolic free calcium (Ca2+)-levels act via receptor coupled G-proteins, involving activation of phospholipase C (PLC) and hydrolysis of phosphatidylinositol 4,5-bisphosphate. Activation of the inositol signal transduction pathway that precedes Ca2+ ion mobilization is a well accepted signaling pathway in endothelial cell eicosanoid synthesis. This study was designed to examine possible involvement of phosphoinositides in the effects of oxygen free radicals on Ca2+ liberation and eicosanoid synthesis in human umbilical venous endothelial cells (HUVEC). Hydrogen peroxide (H2O2) was chosen as oxygen radicals generating agent. Stimulation of HUVEC with H2O2 (0.1 mmol/l) led to significant rises in inositol phosphate and diacylglycerol (DAG) levels within 300 seconds and an inhibition of Ca2+ release from internal stores. Eicosanoid formation was detectable despite unchanged levels of cytosolic free Ca2+ and no detectable activation of membrane associated phospholipase A2 (PLA2). This suggests that eicosanoid formation may be mediated through the activation of a Ca2+ independent, cytosolic 40 kDa PLA2 isoenzyme and that DAG could serve as an alternative source for arachidonic acid and seems to sensitize a cytosolic PLA2.

Cells, Cultured↗

Immunohistochemical detection of CD44 splice variant expression in premalignant lesions of the cervix and benign cervical epithelium.

The expression of specific CD44 splice variants in malignant tumors has been shown to be associated with metastasis and poor prognosis. In previous studies we have detected aberrant expression of the transmembranous cell adhesion molecule CD44 in cervical cancer. Therefore, we now focus on its role in intraepithelial dysplastic lesions of the cervix. Forty-five cervical intraepithelial neoplasias (CIN), grades I to III, were investigated immunohistochemically for three different splice variants of CD44 (v5, v6, and v7-8). A negative correlation of CD44v5 (Kendall correlation coefficient r = -0.25, P < 0.05) expression with the grade of CIN was found. In normal squamous epithelium of the cervix, the staining reaction of CD44v5 was confined to the basal and the parabasal cell layers. In dysplastic lesions a diffuse and weaker staining pattern of the entire epithelium was observed. Our data suggest a loss of CD44v5 epitope during dysplastic transformation. It seems that expression of CD44 splice variants is not a continuous process in the natural history of cervical cancer, and the pattern of CD44 splice variant expression is changed during carcinogenesis.

Cervix Uteri↗

The fast-reacting fetal fibronectin test: a screening method for better prediction of the time of delivery.

OBJECTIVE: Our aim was to determine from what time onward fetal fibronectin is consistently detectable in the cervicovaginal secretions before delivery and to what extent the actual time of delivery can be better determined by this procedure than by the sole use of the Bishop score. STUDY DESIGN: A fast-reacting fetal fibronectin test was performed on 206 women on their expected date of confinement. In addition, the cervical status was evaluated with use of a modified Bishop score. Follow-up evaluations were subsequently carried out in the course of the routine examinations. RESULTS: Women with a positive fetal fibronectin test result and a high Bishop score were delivered after a median of 1.7 days. Conversely, women with a negative fetal fibronectin test result and a low Bishop score were delivered after a median of 7.1 days. CONCLUSION: Determination of fetal fibronectin in combination with the Bishop score makes it possible to predict the actual time of delivery with a greater degree of accuracy.

Cervix Uteri↗