Doris Pieber

Tumor angiogenesis as a prognostic factor in ovarian carcinoma

The growth of a malignant tumor requires the formation of new capillaries. Quantification of these microvessels is difficult. The purpose of this study was to establish an objective technique for quantifying angiogenesis and to evaluate whether microvessel quantity may predict tumor aggressiveness in patients with ovarian carcinoma.

Five-year results after anti-incontinence operations

OBJECTIVE This study was undertaken to evaluate continence rates 5 years after anterior colporrhaphy, anterior colporrhaphy with needle suspension of the bladder neck, and Burch colposuspension. STUDY DESIGN Among 544 women with stress incontinence who were operated on between 1989 and 1993, 327 women (60%) underwent clinical and urodynamic reevaluation 5 years after the operation. Choice of surgical procedure was made on the basis of clinical and urodynamic findings and of physician preference. Continence was defined as no loss of urine during cystometry or during coughing with the bladder filled to 300 mL. RESULTS The 327 patients underwent a total of 334 operations. The objective overall continence rates at 5 years were 61% (65/107) after anterior repair, 49% (59/121) after anterior repair with needle suspension, and 79% (84/106) after Burch colposuspension. Continence rates after anterior colporrhaphy were 82% (32/39) among patients with mild stress incontinence but 49% (33/68) among those with moderate or severe incontinence (P <.02). Continence rates among patients with moderate or severe incontinence were 49% (59/121) after anterior repair with needle suspension and 79% (84/106) after the Burch operation (P <.02). CONCLUSION Anterior colporrhaphy can cure mild stress incontinence but is inadequate to correct severe incontinence. Additional needle suspension may be of benefit for patients with moderate to severe incontinence. Abdominal colposuspension is superior to the vaginal operations for long-term cure of stress incontinence.

Pressor and mesenteric arterial hyporesponsiveness to angiotensin II is an early event in haemorrhagic hypotension in anaesthetised rats

OBJECTIVE Vascular responsiveness to vasoconstrictors is known to be attenuated in haemorrhagic shock. In this study we assessed the temporal development and the underlying mechanisms of haemorrhage-induced vascular hyporeactivity to pressor agents. METHODS In phenobarbital-anaesthetised rats hypotension was induced by graded haemorrhage (8 ml blood total). Sham-manipulated rats served as controls. Blood flow (BF) was recorded with ultrasonic transit time flow probes. RESULTS Following haemorrhage mean arterial pressure (MAP) fell by 25-45 mm Hg and was accompanied by a reduction in mesenteric BF without any alteration of mesenteric vascular conductance (VC). While pressor responses to arginine vasopressin remained unaltered, hyporesponsiveness to phenylephrine (10 nmol kg-1) developed 120-180 min after hypotension had been induced. Pressor and mesenteric constrictor responses to angiotensin II (30 pmol kg-1) became significantly blunted as early as 60 min post haemorrhage. The hypotensive effect of an angiotensin1 receptor antagonist, telmisartan (1 mg kg-1), was likewise blunted 3 h after haemorrhage. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg kg-1) exaggerated the hypotensive reaction to haemorrhage but did not prevent the development of angiotensin II hyporesponsiveness. In contrast, the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (10 mg kg-1), as investigated 3 h post haemorrhage, restored the systemic pressor responses to angiotensin II and phenylephrine as well as the mesenteric constrictor responses to phenylephrine to normal level and diminished the mesenteric hyporesponsiveness to angiotensin II. Glibenclamide (20 mg kg-1), an inhibitor of ATP-sensitive K- channels given 180 min post haemorrhage, partially reversed haemorrhage-induced hypotension but did not modify angiotensin II hyporesponsiveness. CONCLUSION Systemic pressor responsiveness and mesenteric arterial reactivity to endogenous and exogenous angiotensin II is selectively impaired at an early stage of haemorrhagic hypotension. This phenomenon partially involves NO and is not related to ATP-sensitive K+ channels.

Body mass index and outcome of incontinence surgery

OBJECTIVE To analyze the influence of body mass on the outcome of surgery for urinary incontinence. METHODS Among 291 women operated on for stress incontinence, 187 (64%) were available for follow-up at 5 years. Eighty women had anterior colporrhaphy, 49 anterior colporrhaphy with needle suspension of the bladder neck, and 58 Burch colposuspension. Body mass index was calculated preoperatively and at follow-up. Women were classified as being of normal weight (body mass index [BMI] 20-25), overweight (BMI 26-30), or obese (BMI greater than 30). Reported continence rates were analyzed according to BMI for each operation and the BMIs of continent patients were compared with those of incontinent patients. RESULTS The continence rates at 5-year follow-up for anterior colporrhaphy, anterior colporrhaphy with needle suspension of bladder neck, and Burch colposuspension were 58, 51, and 86%, respectively (P < .001). The continence rates did not differ significantly among the three BMI groups for each procedure. A statistical power of 26% was found for the hypothesis that the outcome of the procedures does not depend on BMI. The preoperative and postoperative BMIs of continent and incontinent women for each procedure did not differ significantly. CONCLUSION We did not find preoperative obesity to be a risk factor for failure of incontinence surgery, but the power of our study was limited.

Pelvic floor exercise alone or with vaginal cones for the treatment of mild to moderate stress urinary incontinence in premenopausal women

The authors compared intensive pelvic floor exercise alone (A) with intensive pelvic floor exercise plus vaginal cones (B) in premenopausal women with mild to moderate stress urinary incontinence. Forty-six patients (mean 43±6 years) were randomized into two training groups and treated for 3 months. Pre- and post-therapy urethral pressure profiles at rest and under stress and subjective results were obtained from 29 patients. The subjective improvement rate of the compliant patients after 12 weeks was 85% in group A and 84% in group B. When the dropouts (9 in group A and 8 in group B) were included in the subjective results an overall improvement rate of 48% in group A and 52% in group B was obtained. In group A one pressure transmission ratio (PTR) improved significantly at 6 weeks and the position of maximum urethral closure pressure was shifted proximally at 12 weeks. In group B one PTR in the midurethra was improved significantly at 6 weeks. The other urodynamic parameters were unchanged. There were no differences between groups A and B in subjective results or urodynamic findings. These results suggest that intensive pelvic floor exercise with or without vaginal cones improves the symptoms of mild to moderate stress incontinence in about 85% of premenopausal women, but that it has little effect on urodynamic parameters. Vaginal cones provided no additional benefit but may be useful for women for whom closely supervised pelvic floor exercise is not available.

Inhibition by Female Sex Steroids of Peristalsis in the Guinea Pig Small Intestine

Aims: The effects of steroid hormones on propulsive peristalsis in the intestine were investigated in order to compare their adverse effect profile on this clinically most important motor pattern. Methods: Peristalsis in isolated segments of the guinea pig small intestine was triggered by luminal distension and recorded via the peristalsis-associated changes of the intraluminal pressure. Drug effects on muscular activity were investigated in a circular muscle preparation of the ileum. Results: Estradiol and progesterone, but not testosterone, hydrocortisone or cholesterol (each at 3–30 µM), caused a prompt and concentration-related increase in the peristaltic pressure threshold at which propulsive muscle contractions were elicited. Mifepristone (RU-486; 30 µM) did not prevent the inhibitory effect of progesterone, but blocked peristalsis per se. Pharmacological blockade of inhibitory neural pathways with NG-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), naloxone (opioid receptor antagonist), apamin or suramin plus pyridoxal phosphate-6-azophenyl-2′,4′-disulphonic acid (P2 purinoceptor blockers) counteracted the inhibitory effect of submaximally (10 µM), but not maximally (30 µM), effective concentrations of progesterone. Estradiol and progesterone depressed circular muscle contractions evoked by cholecystokinin octapeptide to a larger degree than responses to the tachykinin NK1 receptor agonist GR-73,632. Conclusion: The peristaltic motor inhibition caused by sex steroids at micromolar concentrations arises primarily from a depressant action on intestinal muscle activity and may be particularly relevant for high-dose regimens of mifepristone.

TIMING OF URETHRAL PRESSURE PULSES BEFORE AND AFTER CONTINENCE SURGERY

In continent women, urethral pressure with stress events has been found to rise approximately 200 msec before pressure in the bladder begins to rise. We studied the time difference in incontinent women, women after successful and unsuccessful incontinence procedures, and continent women, to evaluate the timing of urethral pressure rises in correlation with continence status. We analyzed the urodynamic data of 20 incontinent patients before and after successful or unsuccessful (n = 10 each) Raz needle suspension. Ten continent women served as controls. The time difference between onset of the pressure increase in the urethra and in the bladder was noted before and after surgery. In all 10 continent women the pressure increase in the urethra started to rise approximately 160 msec before the pressure increase in the bladder. In 16 of 20 incontinent patients the pressure in the urethra and bladder rose simultaneously. Successful antiincontinence procedures restored the early onset of urethral pressure increases. Unsuccessful operations did not produce this effect. Successful antiincontinence operations permit timely compression of the urethra. This timely compression is associated with continence. Neurourol. Urodynam. 17:19–23, 1998.

Numerical chromosomal aberrations of chromosome 1 and 7 in dysplastic cervical smears.

Cervical smears with Papanicolaous staining (PAP) reveal only morphological characteristics of epithelial cells of the cervix uteri. Since chromosomal aberrations are known to play a role in malignant transition, we analyzed cervical smears for numerical changes of the chromosomes 1 and 7 with fluorescence in-situ hybridization to probe for a diagnostic value of these chromosomes in the characterization of cervical dysplasia. Cervical smears were collected from 21 patients with suspect histology of curettage or biopsy specimen, 14 of them having been subsequently graded as cervical intraepithelial neoplasia (CIN) III and 5 as CIN II. Nineteen normal cervical smears (PAP I-II) served as controls. Smears were hybridized with chromosomal enumeration probes for chromosome 1 and 7. Disomic cells (2 copies of chromosome 1 and 7) were decreased in the CIN II (63%) and CIN III group (57%) with respect to the control group (77%). Cells with 3 signals for chromosome 7 were significantly more frequent in the CIN III and the CIN II group than in the control group (6.7, 6.4 and 0.7%, respectively). Only the CIN II group (10%), but not CIN II (6%), showed a significant trisomy for chromosome 1 as compared with the controls (3.8%). A close correlation between the incidence of trisomy 1 or 7 and PAP grading was observed. PAP III-IIID smears with high trisomy 1 counts corresponded to CIN III histology, while all CIN II patients were PAP III-IIID with low incidence of trisomy 1. We conclude that trisomy of chromosome 7 is a feature of cervical dysplasia and seems to be an early event in dysplastic transition. In contrast, trisomy of chromosome 1 is observed only in high grade dysplasia and may be a marker for pre-malignant lesions.