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Biomedical subjects

H Koelbl

Publications and source records attributed to H Koelbl.

At least 55 records · Page 3Linked to original sources

Serum CD44 splice variants in cervical cancer patients.

Aberrant expression of the cell adhesion molecule CD44 has been detected in human tumours and has been shown to be associated with metastasis and poor prognosis in human malignancies. We evaluated serum levels of different soluble CD44 molecules (CD44 standard form and CD44 splice variants v5 and v6) in cervical cancer patients stage IB to IIIB. Two-hundred three serum samples were analysed. Serum levels of CD44st and CD44v5 showed no significant correlation with the presence or absence of cervical cancer. The splice variant CD44v6 showed a mean concentration of 227.3 +/- 90.9 (minimum 71.4, maximum 543.9) ng/ml when tumour was present and a mean concentration of 198.7 +/- 135.4 (minimum 67.2, maximum 696.3) ng/ml in cases of complete remission (P-value = 0.0001). However, in this preliminary study the sensitivity/specificity characteristic of CD44v6 was poor.

Adenocarcinoma↗

Cytokeratin subunit 19 measured by CYFRA 21-1 assay in follow-up of cervical cancer.

The purpose of this study was to evaluate the serum tumor markers CYFRA 21-1 and squamous-cell carcinoma antigen (SCC) in the follow-up of squamous-cell cervical cancer patients. One hundred-ninety-three serum samples, which were collected pretherapeutically and during follow-up of 30 patients suffering from squamous-cell cervical cancer FIGO stage III, were analyzed for SCC and CYFRA 21-1. Cutoff values for SCC and CYFRA 21-1 were 3 and 3.3 micrograms/liter, respectively. Fifteen cases were keratinizing and 15 nonkeratinizing squamous-cell carcinomas. Serum tumor marker results were correlated to the results of the clinical and radiologic examinations. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum SCC and serum CYFRA 21-1 for the whole study group and separately for the keratinizing and nonkeratinizing squamous-cell carcinoma group. Sensitivity, specificity, PPV, and NPV of serum SCC were 66, 91, 93, and 60%, respectively. Serum CYFRA 21-1 showed a sensitivity of 63%, specificity of 96%, PPV of 96%, and NPV of 59%. The combination of SCC and CYFRA 21-1 increased the sensitivity to 78%, with a specificity, PPV, and NPV of 87, 91, and 69%, respectively. In keratinizing squamous-cell carcinoma serum SCC, CYFRA 21-1 and the combination of both had a sensitivity of 76, 64, and 85%, respectively. In nonkeratinizing squamous-cell carcinoma sensitivity was 58, 61, and 72%, respectively. The detection of cervical cancer recurrences with SCC is improved by the combination with CYFRA 21-1. Especially in nonkeratinizing squamous-cell carcinoma CYFRA 21-1 showed promising results.

Antigens, Neoplasm↗

Splice variants of CD44 in human cervical cancer stage IB to IIB.

Aberrant expression of the cell adhesion molecule CD44 has been detected in human tumors and the expression of specific CD44 isoforms (splice variants) has been shown to be associated with metastasis and poor prognosis in human malignancies. We used three different variant exon sequence-specific murine monoclonal antibodies to epitopes encoded by exon v5, exon v6, or exon v7-v8 of human variant CD44 to study the expression of CD44 splice variants by immunohistochemistry in human cervical cancer. One-hundred five patients with surgically treated squamous cell carcinomas of the cervix stages IB to IIB were included in the study. CD44 splice variants CD44v5, CD44v6, and CD44v7-8 were detected in 70, 67, and 26%, respectively. Tumors expressing exon v6 had significantly more often metastasized to the pelvic nodes (58 vs 79%, P = 0.04). Expression of exon v6 was significantly correlated with a greater probability of vascular space invasion (73 vs 50%, P = 0.04) and a significantly lower rate of inflammatory stromal reaction (48 vs 78%, P = 0.004). Patients suffering from tumors expressing splice variant CD44v6 showed poorer overall survival (P = 0.03). In cases with negative pelvic lymph nodes we found a poorer prognosis when tumors expressed CD44v6 (P = 0.01) or CD44v7-8 (P = 0.02). Among the investigated CD44 splice variants expression of exon v6 is the most promising prognostic marker in surgically treated cervical cancer.

Adult↗

Differential diagnosis of detrusor instability and stress-incontinence by patient history: the Gaudenz-Incontinence-Questionnaire revisited.

OBJECTIVE: To evaluate the validity of the Gaudenz-Incontinence-Questionnaire in the differential diagnosis of genuine stress-incontinence and detrusor instability. DESIGN: Diagnoses based on questionnaire-results were compared to those following complete urogynecologic assessment including urodynamics in 1938 patients with lower urinary tract symptoms. RESULTS: Sensitivity and specificity for diagnosis of stress-incontinence were 0.559 and 0.447, respectively, for detrusor instability 0.615 and 0.563, respectively. CONCLUSION: The low sensitivity and specificity of the test do not justify its use as a diagnostic tool in patients with urinary incontinence. These results show that the scores may be misleading in a large proportion of patients and should not therefore be the only determinant of diagnosis, nor should strategies be based on history alone.

Adult↗

Imaging of the lower urinary tract.

Review of the current literature indicates that the application of various ultrasound techniques plays the most important role in research of imaging of the lower urinary tract. Whereas sonographic urethrocystography by perineal, introital, or vaginal ultrasound has replaced radiography in routine clinical use, more detailed information about the urethra and periurethral tissues has been obtained by three-dimensional sonography and intraluminal high frequency ultrasound. Magnetic resonance imaging is emerging as the newest technique in this field, and has the potential to expand our knowledge of interactions of the lower urinary tract and the pelvic floor.

Abdomen↗

Influence of catheterisation on the results of sonographic urethrocystography in patients with genuine stress incontinence.

Using introital sonography as an alternative to lateral chain urethrocystography during urodynamic studies, a prospective investigation was carried out in 47 patients with lower urinary tract complaints, to determine the correlation of sonographic assessment with and without bladder catheterisation. The apparent location of the bladder neck in relation to the pubic symphysis and measurements of the posterior urethrovesical angle at rest and during straining during cystometry with and without intravesical urodynamic pressure transducers were determined. In 22 (46.8%) patients the bladder neck at rest was below the lower edge of the symphysis. This finding was not influenced by the presence of a catheter. Correlation coefficients (r) for posterior urethrovesical angles at rest and during straining measured with and without catheters were 0.95 (95% confidence limits 0.92-0.98; P < 0.01) and 0.98 (95% confidence limits 0.96-0.99; P < 0.01), respectively. The coefficients of determination (r2) at rest and during straining were 0.92 and 0.95, respectively. Sonography with and without cystometry equipment in place gave similar results.

Adult↗

Direct evidence of a parathyroid related protein gradient between the mother and the newborn in humans.

Umbilical cord plasma has increased parathormone (PTH)-like bioactivity in comparison with that in maternal plasma, but suppressed PTH levels. Previous attempts to detect elevated levels of PTHrP(1-34) in the umbilical cord were unsuccessful, whereas PTHrP was detected by immunohistochemistry in both fetal parathyroid glands and placental membranes. At the time of delivery, plasma samples were drawn simultaneously from 47 normal mothers (mean age, 26 years) and from the umbilical cord of 25 female and 22 male newborns and assessed for calcium adjusted for albumin, magnesium, creatinine, intact PTH and PTHrP. PTHrP was measured using a new 2-site immunoradiometric assay recognizing separately 1-40 and 60-72 residues with a sensitivity of 0.3 pmol/l. Mean (+/- S.D.) plasma calcium values were 2.35 +/- 0.10 in the mothers versus 2.63 +/- 0.12 mmol/l in the newborns (P < 0.001). PTH values were significantly higher in the mothers, as expected (22.3 +/- 14.8 vs. 6.2 +/- 0.9 pg/ml). In contrast, PTHrP values were significantly higher in the newborns (1.50 +/- 0.39 versus 0.84 +/- 0.28 pmol/l, P < 0.001). Only 1/47 mother had a PTHrP level higher than her child (0.9 vs. 0.8 pmol/l). Only 10/47 mothers had PTHrP higher than 1 pmol/l whereas only 1/47 newborn had a value below 1 pmol/l. There was no correlation between Ca and PTHrP in either group. Serum creatinine values were all within the normal range. Serum magnesium levels were not different between the mothers and the children.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

Superparamagnetic particles as oral contrast medium in magnetic resonance imaging of patients with treated ovarian cancer--comparison with plain MRI.

In 23 patients with treated ovarian cancer, 24 magnetic resonance (MR) examinations of the abdomen and pelvis were performed before and after administration of an oral superparamagnetic contrast medium. Depiction of bowel loops was judged sufficient in 47% with plain scans and in 85% with enhanced scans. Minor artefacts attributed to the agent were noted in 32% of examinations and were classified as disturbing in 8%. The diagnostic information obtained after contrast enhancement was estimated to be superior to that from plain MRI in 20% of patients. The use of oral contrast medium did not alter the MR diagnosis of "tumour recurrence" or "disease-free" in any patient. Our results suggest that superparamagnetic iron oxide is an effective and reliable approach to negative bowel contrast enhancement, increasing the confidence level when distinguishing intestines from solid structures.

Adult↗

Levator ani muscle morphology and recurrent genuine stress incontinence.

OBJECTIVE: To assess the impact of levator ani muscle morphology on the outcome of patients with genuine stress incontinence undergoing reconstructive surgery of the pelvic floor. METHODS: A follow-up investigation was performed on 30 patients from a previous study, who had undergone hysterectomy with combined anteroposterior vaginal repair for pelvic floor relaxation and genuine stress incontinence. Biopsy specimens of the pubococcygeal muscle had been obtained during posterior colporrhaphy and subsequently evaluated for evidence of striated muscle tissue. Eleven patients had striated muscle tissue in the biopsy specimens (group A), whereas 19 subjects did not (group B). Before operation and at 41 months (range 37-44) after operation, the patients underwent urodynamics, perineal sonography, and perineometry. RESULTS: At follow-up, all patients in group A were continent, whereas ten of 19 patients (53%) in group B showed recurrent genuine stress incontinence (P < .01). Compared with group B (48.5 +/- 21.9%), group A patients (71.8 +/- 16.5%) had a significantly higher abdominal pressure transmission ratio at follow-up (P = .02). At postoperative perineal sonography, group A patients (107.7 +/- 14.0 degrees) showed a significantly smaller retrovesical angle during straining than did group B patients (134.6 +/- 25.9 degrees) (P < .01). CONCLUSION: The levator ani muscle morphology has prognostic importance for the outcome of patients with genuine stress incontinence undergoing anteroposterior vaginal repair.

Female↗

Treatment with biologic response modifiers in patients with ovarian cancer.

The therapeutic and immunomodulating potential of biological response modifiers (BRM) such as OK-432 (a streptococcal preparation) and recombinant interferon gamma (rIFN-gamma) has been evaluated in 15 patients with advanced chemotherapy resistant ovarian cancer, presenting malignant ascites and/or pleural effusions. OK-432 was injected intracavitary in 10 patients in increasing doses from 0.2 up to 7.5 mg weekly. Five women were treated intracavitary with rIFN-gamma twice a week. The initial dose was 0.1 mg/m2 which was raised up to 12 mg/m2 over 6 weeks. With OK-432 a complete response was achieved for 14.1 + 8.9 months in 4 patients, a partial response for 1.7 + 0.3 months in 3 patients. The survival time of the 4 responders was significantly longer (21.1 + 8.3 months) than the survival time of the patients with partial or no response (4.9 + 2.7,4.1 + 2.3 months, respectively). In the rIFN-gamma therapy group, we found a partial response in one and no response in 4 patients. Toxicity observed under OK-432 and rIFN-gamma was minimal in all patients, suggesting a lack of systemic effect of intracavitary-applied BRM. With both agents, augmentation of certain immune responses, especially in the peritoneal cavity and to a lesser extent in the peripheral blood, has been documented. In 5 patients treated with OK-432, we found an overall augmentation of the effusion macrophage killer activity. rIFN-gamma augmented natural killer activity in 2 of 3 patients.

Aged↗

Reliability of the urethral closure pressure profile during stress in the diagnosis of genuine stress incontinence.

Urethral pressure profile (UPP) measurements were recorded during stress using the method of Brown and Wickham in 981 patients with lower urinary tract symptoms. This procedure was used to identify patients with genuine stress incontinence (GSI). A clinical stress test in the supine and erect position served to confirm urinary leakage. GSI was diagnosed in 661 patients. (67%), whereas no incontinence was demonstrable in 320 (33%). UPP during stress has a high sensitivity (93.3%) and specificity (82.5%). Compared with other urodynamic investigations, the ease with which it can be performed at the same time as other urodynamic procedures makes a reliable diagnostic adjunct in the assessment of patients with GSI.

Cough↗

Assessment of female urinary incontinence by introital sonography.

By the use of a vaginal sector scanner, placed to the vaginal introitus (introital sonography), we studied the static and dynamic function of the urethrovesical region in patients with genuine stress incontinence and detrusor instability. Patients with genuine stress incontinence (n = 25) revealed either an increase of the retrovesical angle or the angle of inclination associated with a descent of the bladder neck during coughing. Opening of the bladder neck during cystometry, showing an increase of the detrusor pressure, was observed in patients with motor urge incontinence (n = 10). Application of the technique is recommended in patients with stress incontinence undergoing surgery for objective intraoperative assessment of successful reformation of the urethrovesical junction, irrespective of the surgical procedure. Compared with radiologic techniques, introital sonography has many advantages with no radiation exposure and with minimal inconvenience to the patient.

Female↗

Diagnostic versus therapeutic second-look surgery in patients with ovarian cancer.

Between August 1982 and January 1988, 82 patient with epithelial ovarian cancer underwent second-look laparotomy. Before second-look surgery, 37 patients (45%) were in clinical complete remission. Eleven of these women who had previously received complete surgery received a diagnostic second-look operation. Whereas the clinical diagnosis of a complete response was confirmed by second-look procedure in eight of these patients, positive tumour findings were still evident in four women. The other 26 women who did not have clinical evidence of disease underwent staging second-look laparatomy to complete primary surgery. However, 11 patients revealed macroscopic evidence of tumour. In addition, the second-look operation was classified as a staging procedure in two women despite progressive disease classified preoperatively, but with negative intra-abdominal tumour findings. A therapeutic second-look laparotomy was performed in 37 patients with clinical evidence of disease to remove as much tumour as possible. Second-look laparatomy as a palliative procedure was necessary in six patients. Considering the type of second-look procedure, the 39 patients (48%) who underwent a diagnostic or staging procedure revealed a significantly longer median survival time of 62 months compared with the 43 women (52%) who underwent therapeutic or palliative second-look surgery and had a median survival of 19 months (P less than 0.0003, Log Rank Test). In patients with positive tumour findings at the time of second-look surgery, therapeutic cytoreduction was not associated with an improved survival time. We conclude that second-look surgery should be performed only in patients who are clinically free of disease to evaluate their intraperitoneal tumour status.

Adult↗

Influence of delivery on plasminogen activator inhibitor activity.

Plasminogen activators initiate the fibrinolytic system by conversion of the proenzyme plasminogen to the active fibrin degrading enzyme plasmin. Plasminogen activator inhibitors inhibit the effects of both plasminogen activators. Uncomplicated pregnancies are accompanied by hypercoagulability and an increased risk of thromboembolic disease. Thrombosis is rare in the first trimester and most events are noted in the last trimester. Therefore, we studied the fibrinolytic system at the end of pregnancy and in the puerperium. Plasma concentrations of urokinase plasminogen activator (u-PA/competitive radioimmunoassay), tissue type plasminogen activator (t-PA/sandwich ELISA) and plasminogen activator inhibitor (PAI/functional assay) were determined in 44 women (age: 24.3 +/- 4.3 years) with normal pregnancy near term. Plasma samples were collected before the onset of labour and 1, 2, 3, 4 and 5 days after delivery. Compared with an age-matched non pregnant control group (8.3 +/- 3.94 U/ml) significantly increased PAI activity (12.13 +/- 4.79 U/ml - p less than 0.005) was measured before delivery with a subsequent significant decrease (8.13 +/- 1.97 U/ml) to normal values on day 1 after delivery; plasma u-PA and t-PA antigen levels remained unchanged. Placental weight and birth weight had no influence on plasma levels of both plasminogen activators.

Adult↗

A new method for sonographic urethrocystography and simultaneous pressure-flow measurements.

By the use of a vaginal scanner and simultaneous pressure-flow measurements, we developed a new method to study bladder and urethral function. During urodynamic pressure measurements, a vaginal scanner was positioned adjacent to the vulva just underneath the external urethral orifice to scan the bladder, the vesicourethral junction, and the urethra. This technique was termed "introital sonography." Twenty patients with the symptom of "loss of urine" and ten healthy volunteers without urinary symptoms were studied. Introital sonography displayed the bladder, the urethra, and the symphysis in all women. No incontinence was demonstrable in the healthy control group. Opening of the bladder neck was always visible during micturition, and a normal flow pattern could be observed in all healthy women. In five patients with detrusor instability, opening of the bladder neck was found during cystometry, displaying isolated detrusor contractions. Fifteen patients with genuine stress incontinence demonstrated marked descent of the vesicourethral junction under stressful situations. For the diagnosis of detrusor instability, sonographic visualization of bladder neck opening confirms the entity of isolated detrusor contractions during cystometry and thus helps to exclude tonometric artifacts. Introital sonography not only confirms the diagnosis of genuine stress incontinence by accurately demonstrating the abnormal vesicourethral anatomy, but also provides information that is essential for selecting the proper operative procedure. The lack of radiation exposure and contrast medium makes this inexpensive technique most useful for long-term video pressure-flow studies in patients with bladder dysfunction.

Female↗

Morphologic and functional aspects of pelvic floor muscles in patients with pelvic relaxation and genuine stress incontinence.

Thirty women (mean age 49 years; range 33-74) with mild to moderate pelvic relaxation and genuine stress incontinence underwent preoperative urodynamic studies. Biopsy specimens from the levator ani muscles during vaginal hysterectomy and repair were evaluated for the number and the individual diameters of type I (slow-twitch) and type II (fast twitch) fibers. Biopsies from 11 women revealed striated muscle tissue, whereas no muscle tissue was observed in the other 19. Compared with patients without muscle tissue, subjects with positive muscle findings showed significantly higher transmission ratios (55.0 +/- 23.4 versus 32.9 +/- 22.1%; P less than .05). Mean diameter and counts of types I and II muscle fibers decreased significantly with age (P less than .05). Urethral closure pressure during stress significantly increased with mean diameter of type II muscle fibers (P less than .05). In contrast to patients with severely damaged pelvic floor muscles, the presence of slow-twitch fibers is associated with improved support of the pelvic viscera, especially under conditions leading to intra-abdominal pressure rise. The presence of fast-twitch fibers improves the periurethral continence mechanism, resulting in an increase of urethral closure pressure during stress.

Biopsy↗

A comparative study of mucin-like carcinoma-associated antigen (MCA), CA 125, CA 19-9 and CEA in patients with ovarian cancer.

A mucin-like carcinoma associated antigen (MCA), which is recognized by the monoclonal antibody b-12, was found to be elevated in sera of breast cancer patients. Since an immunohistochemical reaction of the monoclonal antibody b-12 was found in epithelial tumors of the ovary we investigated MCA serum levels in 50 patients with ovarian cancer (mean age 59 years, range 31-81 years). In addition, CA 125, CA 19-9 and CEA were determined to compare sensitivity, specificity and the predictive value of the positive test of each parameter used in this study. Blood samples were obtained in 20 patients with progressive disease and in 30 patients during disease free intervals. The MCA serum levels of patients with progressive ovarian cancer (mean +/- SD: 14.7 +/- 14.6 U/ml) did not differ significantly from those of patients in remission (mean +/- SD: 8.2 +/- 5.3 U/ml) or from values of a healthy control group (mean +/- SD: 7.7 +/- 3.8 U/ml, n = 70). Women with progressive disease displayed significantly higher CA 125 (p less than 0.0001) and CEA (p less than 0.0063) serum levels than patients in remission. No significant difference was found for CA 19-9 in patients with ovarian cancer, irrespective of the clinical status. Considering marker surge and tumor progression, the highest sensitivity was found for CA 125 (75%). Sensitivities of the other markers were significantly lower and reached only 25-35%. The predictive value of elevated marker levels as well as specificity of the marker substances were similar. Sensitivity could be extended to 90% if elevation of CA 125, CA 19-9, CEA and MCA were taken into consideration, however specificity was lowered by using this marker combination.

Antibodies, Monoclonal↗

Cystosonography in the staging of gynecological malignancy.

Five patients with carcinoma of the cervix and one with carcinoma of the vagina were examined by both cystoscopy and endosonography. Both techniques revealed malignant infiltration of the bladder in 4 patients. In the other 2 cystoscopy showed an intact bladder mucosa despite cystosonographic evidence of invasion of the bladder wall by tumor.

Aged↗