Photodetector sensitivity level and heidelberg retina flowmeter measurements in humans.

PURPOSE: In vitro models suggest that Heidelberg retina flowmeter (HRF) measurements are affected by changes in photodetector sensitivity. We measured blood flow in a single volume of human retinal tissue in vivo at various sensitivity (DC) levels. METHODS: The peripapillary retinal regions of 12 normal subjects were examined by HRF under five different sensitivity settings: (1) average DC range below 100; (2) average DC range below 125; (3) average DC range near 150 (normal sensitivity); (4) average DC range above 175; and (5) average DC range above 200 or extremely overexposed. The distributions of flow values were examined by pointwise analysis. All pixels from a common tissue location were analyzed, and the effect of their brightness on the flow measurement was evaluated by ANOVA with Fisher's protected least significant difference model. RESULTS: ANOVA analysis of image DC level showed that significantly different DC levels were achieved for each of the five sensitivity settings (P < 0.0001). Flow values decreased with increasing DC for each of the 25th percentile, 50th percentile (P: < 0.0001 for each), 75th percentile (P: = 0.0026), 90th percentile (P: = 0.0216), and mean (P: = 0.0004) flow values. The percentage of pixels with values of zero (avascular tissue) increased with increasing photodetector sensitivity (P< 0.0001). CONCLUSIONS: Improper sensitivity settings alter the detected percentage of avascular tissue and the blood flow measurements in tissue containing capillaries. Consistent assessment of retinal blood flow requires consistent photodetector sensitivity settings between longitudinal images.

New neuroretinal rim blood flow evaluation method combining Heidelberg retina flowmetry and tomography.

AIM: Accurate Heidelberg retina flowmeter (HRF) measurements require correct manual setting of the HRF photodetector sensitivity. The neuroretinal rim produces a weak signal relative to the peripapillary retina. A newly developed HRF alignment and sensitivity protocol, capable of accurate rim measurement, was investigated. METHODS: 18 eyes of nine healthy volunteers were examined by HRF. Three images of each eye were taken using three different imaging methods. Method 1: a conventional image (optic nerve head centred image with photodetector sensitivity optimised for the strong signal from the peripapillary retina); method 2: the setting of method 1 with photodetector sensitivity optimised for the weak signal from the rim; and method 3: the setting of method 2 with the temporal rim margin tangent to the lateral image border to remove the overpowering signal from the temporal peripapillary retina. The neuroretinal rim was defined by the Heidelberg retina tomograph (HRT). Blood flow and reflectivity values (DC component) in the rim area were compared for the three methods using pointwise analysis. Coefficients of variation of repeated measurements in 12 subjects have been calculated for method 3. RESULTS: The neuroretinal rim area measured by method 1 had a significantly lower brightness compared with method 2 and 3 (p=0.0002 and p=0.0002, respectively). Method 2 provided proper sensitivity for the weak signals of the rim area based on rim tissue DC values; however, this sensitivity setting was too high for the strong signal from the peripapillary retina. Method 3 avoided the strong peripapillary signal with the proper signal from the rim and provided significantly higher flow values of the rim area at 75 and 90 percentile pixels (p=0.0065 and p=0.0038 respectively) compared with method 2. Interobserver repeatability ranged from 16.85% to 21.96% for the different parameters. CONCLUSIONS: Method 3 provides an accurate and reproducible flow measurement of the neuroretinal rim area through proper sensitivity for the weak rim signal, alignment, and removal of the strong temporal signal from the image. This new method is recommended to improve accuracy of blood flow measurement in the neuroretinal rim.

Estrogen-replacement therapy: effects on retrobulbar hemodynamics.

PURPOSE: Estrogen-replacement therapy causes vasodilation and increased blood flow in major peripheral arteries. We examined the role that estrogen may play in enhancing perfusion within the watersheds of several major and minor retrobulbar arteries. METHODS: Postmenopausal women receiving estrogen-replacement therapy (n = 16) were compared with both age-matched women not receiving estrogen (n = 16) and with young women (n = 20). Studies involved color Doppler imaging analysis of flow velocities measured in the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries. RESULTS: In the ophthalmic artery, young women and postmenopausal women receiving estrogen exhibited reduced resistance indexes as compared with postmenopausal women not receiving estrogen (each P <. 001). In contrast, flow velocities in the central retinal artery were similar among the three groups of women. In the posterior ciliary arteries, a different pattern emerged: young women, as compared with either group of postmenopausal women, showed greater peak systolic and end-diastolic velocities at similar resistance index (each P <.05). CONCLUSIONS: Estrogen-replacement therapy in postmenopausal women apparently helps reduce vascular resistance distal to the ophthalmic artery to levels matching those of young women. However, estrogen replacement has little impact on flow velocities in the posterior ciliary arteries. In those vessels, aging per se may reduce perfusion, potentially contributing to the age-dependent risk of major eye diseases, such as glaucoma and age-related macular degeneration.

A repetitive DNA sequence that characterizes human papillomavirus integration site into the human genome is present in vulvar vestibulitis.

OBJECTIVE: To determine the DNA sequence of polymerase chain reaction (PCR) products obtained from surgical specimens of patients with severe vulvar vestibulitis, in order to identify and type the human papillomavirus (HPV)-DNA associated with vulvar vestibulitis. STUDY DESIGN: Fifty three women, referred for dyspareunia and diagnosed as having severe vestibulitis, underwent perineoplasty operation consisting of surgical removal of the sensitive vestibule. PCR analysis using L1 HPV primer was performed, and DNA sequencing of the samples that were found to contain HPV-DNA was undertaken, using the dideoxy chain termination method. RESULTS: Using PCR, HPV-DNA was detected in 31 of 53 tissue specimens (58%). DNA sequencing of 12 HPV-positive PCR products revealed extensive homology to human Alu consensus sequence, albeit not to any known HPV sequence. CONCLUSIONS: The presence of interspersed, repetitive-DNA sequence Alu, which is known to be the preferred site for HPV integration into human genome, in the PCR product reinforces previous observations, suggesting that HPV may have a role in the pathogenesis of vulvar vestibulitis. It further implies a possible integration of the HPV into human DNA in these cases.

Decision-making in the colposcopy clinic--a critical analysis.

OBJECTIVE: To consider the omission of several diagnostic steps from the management of patients with high-grade squamous intraepithelial lesion (SIL) by analyzing the role of each step on the choice of treatment. STUDY DESIGN: Each diagnostic procedure was correlated to the treatment and outcome in 87 women with high-grade SIL. Treatments considered were large loop excision of the transformation zone (LLETZ) cold knife conization, and CO2 laser vaporization. RESULTS: Unsatisfactory colposcopy (P< or =0.01) and positive endocervical curettage (ECC) specimen (P< or =0.01) were essential for choice of treatment. CIN2 diagnoses of the preoperative cervical biopsy were rediagnosed as CIN3 based on the surgical specimen in 57% of the cases. The margins of 33 and 23% of surgical specimens removed by LLETZ or knife conization, respectively, displayed CIN involvement. Forty and 47% of these patients, respectively, later developed recurrent CIN. CONCLUSIONS: Omission of colposcopy and ECC could have resulted in sub-optimal treatment in many cases. Excision by LLETZ or knife conization is recommended for cases of CIN2 and CIN3. Follow up is imperative for patients with involvement of the margins.

Vulvar vestibulitis: physical or psychosexual problem?

OBJECTIVE: To examine whether vestibulitis has a physical or a psychosexual etiology. DATA SOURCES: MEDLINE was searched to retrieve publications dating from January 1981 through June 1998 that evaluated the outcomes of surgical treatment and the psychosexual theory of the origin of vestibulitis. INTEGRATION: Articles were analyzed for methods of subject selection and surgery, surgical outcome, and length of follow-up. RESULTS: A significant decrease in symptoms (complete responses + partial responses) was reported by 89% of 646 women who had perineoplasty for vulvar vestibulitis. Complete resolution of dyspareunia with surgical treatment was reported in 72% of 512 women whose cases were reviewed in studies in which complete responses and partial responses were evaluated separately. Women with vestibulitis did not differ from the normal population with respect to marital satisfaction, psychologic distress, or psychopathology. A suggestion that childhood sexual abuse caused vestibulitis has not been confirmed. The findings of somatization and shyness might be explained as results rather than causes of vulvar vestibulitis. CONCLUSION: We do not agree that vestibulitis is a psychosexual problem and one that should not be treated surgically. A high rate of success can be achieved with proper surgical treatment.

The effect of low dose octreotide administration on renal function and on gene expression of IGF-I axis components in experimental diabetes mellitus.

The present study was undertaken to assess the chronic effects of low dose octreotide (Oc) administration in rats with experimental diabetes mellitus (DM). Metabolic and clearance studies were performed in control normal rats, in rats with streptozotocin-induced DM of 1 week duration and in similar DM rats treated with Oc, 10-20 microg/day. Gene expression of IGF-I, IGF-I receptor (IGF-I R) and IGF-binding protein-1 (IGFBP-1) was examined in renal tissue from normal DM animals and DM animals treated with Oc 10, 20 and 100 microg/day. Seven days of Oc administration, 10 microg/day, in rats with experimental DM, was associated with enhanced hyperglycemia, increased glomerular filtration rate and urinary sodium excretion as compared with untreated DM animals. After a higher Oc dose, 20 microg/day, however, there were no significant changes in renal function and in glycemic control. Significant increases in kidney weight and kidney weight/body weight ratio were seen in DM rats as compared with control intact animals. These changes were not affected by Oc therapy in various doses. Induction of DM was associated with a marked increase in renal IGFBP-1 mRNA expression. There were no significant changes in the expression of IGF-I or IGF-I R mRNA. Oc therapy in a low or high dose did not affect gene expression of IGF-I, IGF-I R or IGFBP-1. Thus, the response to chronic low dose Oc administration of DM rats may vary from enhanced hyperglycemia and hyperfiltration to a lack of change in renal function or in glycemic control. Low dose Oc therapy was not associated with significant variations in renal mass or in the gene expression of IGF-I axis components. These findings are at variance with previously published studies which show a suppressive effect of Oc on renal function and growth in experimental diabetes. This apparent discrepancy may be related to the duration of treatment or to a biphasic physiological effect of Oc when used in different doses.

Persistent vulvar vestibulitis: the continuing challenge.

A continuing challenge in the management of women with vulvar vestibulitis is the patient who has not responded to surgical treatment. The main reason for persistent dyspareunia is failure to excise the sensitive periurethral tissue in the primary operation. In other cases, the Bartholin's glands may be the source of the pain. A low oxalate diet, the administration of interferon, and biofeedback training of the lower pelvic muscles-treatments that are used as a first-choice approach for vulvar vestibulitis, may all work in the postoperative patient. The management of a patient with residual vestibulitis should be conservative, and only when medical measures fail, do we consider additional surgical methods such as Bartholin's gland resection or repeat perineoplasty.

Recombinant human interferon-beta for condylomata acuminata: a randomized, double-blind, placebo-controlled study of intralesional therapy.

To assess the efficacy of a novel glycosylated mammalian cell derived recombinant human interferon-beta (r-hIFN-beta-1a) in the intralesional treatment of genital condylomata acuminata. The study was randomized, double-blind and placebo-controlled. Patients (n=60) with up to 8 distinct condylomata acuminata were randomized to receive either one million international units (IU) of r-hIFN-beta-1a or placebo intralesionally into each lesion, 3 times a week, for a total of 9 occasions. Biopsies were taken from each patient before enrolment to allow human papillomavirus (HPV) testing, and patients were tested for the development of anti-IFN-beta antibodies. Efficacy was assessed by measuring the complete response rate 3 months after treatment. The complete response rate was not significantly better with r-hIFN-beta-1a than with placebo. However, after 3 months, 73.3% of patients treated with r-hIFN-beta-1a had experienced at least a partial response to treatment, compared with 33.3% of placebo-treated patients. At 19 days and 6 weeks, r-hIFN-beta-1a produced a significantly larger reduction in the area of condylomata. Lesions with detectable HPV6 or 11 showed a trend towards a better response rate to treatment with r-hIFN-beta-1a than lesions where no HPV DNA was detected. The treatment was well tolerated. In the 5 patients who developed non-neutralizing anti-IFN-beta antibodies, therapeutic efficacy was not compromised. Intralesional r-hIFN-beta-1a was effective in the reduction of the size of genital condylomata acuminata.

Determining blood pressure in pregnancy. Positional hydrostatic effects.

OBJECTIVE: To evaluate positional hydrostatic effects on blood pressure determination during pregnancy. STUDY DESIGN: We studied 30 normotensive, pregnant women at 34-41 weeks of gestation. Blood pressures were taken in the sitting, left lateral, right lateral and supine positions with a two-minute stabilization period between positions. The bisacromial diameter was measured. Multivariate analysis of variance for repeated measures was used to evaluate the affect of position on blood pressure. RESULTS: Mean systolic pressure in the right arm was 2.6 mm Hg greater than that in the left arm (P < .05). There was no difference between the arms in diastolic blood pressure. Immediate blood pressure in the lower arm was no greater than in the higher arm in lateral positions, and there were no other significant positional effects. Observed blood pressures were significantly different than those theoretically expected on the basis of hydrostatic effects (P < .0001). CONCLUSION: Positional effects on blood pressure in the lateral positions do not appear immediately (within two minutes), indicating that hydrostatic pressure does not account for these changes. The well-documented blood pressure reduction from longer duration in the lateral position does not appear to be an artifact of hydrostatic effect. Repositioning pregnant women in the supine position to have the cuff at the level of the heart is unnecessary and often undesirable when fetal perfusion is an important consideration. We suggest that American Heart Association blood pressure guidelines stating that all measurements be taken with the cuff at the level of the heart to avoid hydrostatic pressure change be revised for pregnancy.

Predicting the outcome of surgical treatment of vulvar vestibulitis.

OBJECTIVE: To identify predictive factors for success or failure of perineoplasty for severe vulvar vestibulitis. METHODS: Seventy-nine women with severe vulvar vestibulitis underwent perineoplasty by a single surgeon during 1992-1994. Sixty (76%) who experienced a complete response were compared with 19 (24%) who had an incomplete response. Using univariate and then multivariate (logistic regression) analysis, the two groups were compared with regard to preoperative demographic, social, and medical variables, as well as physical findings in the vestibule. RESULTS: The complete- and incomplete-response groups were similar in all comparisons except for constant vulvar pain of vestibular origin (in addition to dyspareunia) and the presence of symptoms since first coitus. On multiple logistic regression, these characteristics had odds ratios (and 95% confidence intervals) of 4.97 (1.49, 16.63) and 5.83 (1.74, 19.55), respectively. CONCLUSION: An incomplete response to perineoplasty may be anticipated in women with vulvar vestibulitis associated with dyspareunia since their first episode of intercourse and in those with associated persistent vulvar pain. Treatment approaches other than surgery should be considered for such patients.

Vestibulodynia--a subset of vulvar vestibulitis or a novel syndrome?

OBJECTIVE: Our purpose was to recognize special features of women with both vestibulitis and constant vulvar pain (vestibulodynia) and to determine whether vestibulodynia is a separate disease entity or a subset of vestibulitis. STUDY DESIGN: Ninety-one women with severe vulvar vestibulitis underwent perineoplasty by a single surgeon during 1992 to 1995. Twenty-five (27%) of them who had vestibulodynia were compared with 66 (73%) who had dyspareunia alone. With univariate and then multivariate analysis, the two groups were compared with regard to demographic, social, and medical variables, the presence of human papillomavirus deoxyribonucleic acid, physical findings in the vestibule, and surgical outcome. RESULTS: The vestibulodynia and vestibulitis groups differed in age (30.5 +/- 10.6 years vs 24.7 +/- 6.2 years respectively), as well as in marital status (married, 44% vs 18%, respectively), nonuse of contraception (20% vs 1%, respectively), presence of human papillomavirus deoxyribonucleic acid in the vestibule (80% vs 48%, respectively), and failure of surgical treatment (incomplete response rate, 64% vs 2%, respectively). With multivariate analysis, patients with human papillomavirus deoxyribonucleic acid present in the vestibule have an odds ratio of 5.44 (95% confidence interval, 1.45 to 20.33) of belonging to the group with vestibulodynia, whereas dysuria and age have odds ratios of 3.70 (95% confidence interval 1.09 to 12.55) and 1.14 (95% confidence interval 1.04 to 1.24), respectively. CONCLUSIONS: Vestibulodynia is a unique syndrome in that it affects women who are older than those who have vestibulitis alone and it is associated with human papillomavirus deoxyribonucleic acid, dysuria, and a higher surgical failure rate than that for vestibulitis.

A randomized comparison of prostaglandin E2, oxytocin, and the double-balloon device in inducing labor.

OBJECTIVE: To compare the efficacy of three methods for ripening and dilating the unfavorable cervix for induction of labor. METHODS: Pregnant women having an indication for induction of labor with a singleton vertex fetus, intact membranes, and Bishop score of no more than 4 were randomized to one of three induction methods: intravaginal prostaglandin (PG) E2 tablets (3 mg) followed by a second dose if labor did not start; continuous intravenous oxytocin drip; or the Atad Ripener Device, with inflation of both balloons and removal after 12 hours. For all patients, the cervix was assessed by the same investigator before induction and 12 hours later. RESULTS: Thirty subjects were included in the PGE2 group, 30 in the oxytocin group, and 35 in the Atad Ripener Device group. The postpartum course was comparable in all. The change in Bishop score in the PGE2 and Atad Ripener Device groups was significantly better than in the oxytocin group (median and range of 5[0-9] and 5[0-7], respectively, versus 2.5 [0-9]; P < .01). Cervical dilation more than 3 cm was more frequent in the Atad Ripener Device group compared with both the PGE2 and oxytocin groups (85.7 versus 50 and 23.3%, respectively; P < .01). The trial of induction failed in only two patients (5.7%) in the Atad Ripener Device group, compared with six (20%) in the PGE2 and 16 (53.3%) in the oxytocin groups (P < .001). Mean (+/- standard deviation) induction-to-delivery interval was 21.3 +/- 7.0 hours in the Atad Ripener Device group, 23.2 +/- 12.5 hours in the PGE2 group, and 28.2 +/- 14.7 hours in the oxytocin group. The success rate for vaginal delivery was significantly better in the Atad Ripener Device and PGE2 groups compared with the oxytocin group (77.1 and 70%, respectively, versus 26.7%; P < .01). CONCLUSION: The Atad Ripener Device had a significantly better success rate for cervical dilation and a lower failure rate than those for PGE2 and oxytocin. The PGE2 and Atad Ripener Device groups had better results than the oxytocin group in regard to Bishop score change and induction-to-delivery interval. The Atad Ripener Device may be a superior method for cervical ripening and labor induction in patients with unfavorable cervices.

Perineoplasty compared with vestibuloplasty for severe vulvar vestibulitis.

OBJECTIVE: To evaluate the efficacy of vestibuloplasty (vestibular undercutting without excision) to treat severe vulvar vestibulitis. DESIGN: Prospective randomisation of patients scheduled for surgery to undergo either perineoplasty or vestibuloplasty. Differences in outcome between groups were analysed using Fisher's exact test. SETTING: The Vulvar Clinic and referral centre for vestibulitis, Kupath Holim Health System, Department of Obstetrics and Gynaecology, Carmel Medical Centre, Rapapport Faculty of Medicine, Hatechnion, Haifa, Israel. SUBJECTS: Twenty-one women with vulvar vestibulitis. RESULTS: Vestibuloplasty failed to relieve symptoms in 10 women, while perineoplasty resulted in complete resolution of symptoms in 9/11 women (P < 0.002). CONCLUSIONS: The poor outcome of vestibuloplasty, if also reported by other centres, may render it an unacceptable treatment for vulvar vestibulitis. Vestibuloplasty aims to denervate sensitive vestibular tissue, and its failure may suggest that innervation disturbances are not the main cause of the syndrome.

The effect of metal detector gates on implanted permanent pacemakers.

The effect of metal detector security gates, such as are used in airports, was tested in 103 nonselected pacemaker patients. Various types of single and dual chamber units were examined, using telemetry during the test. Pulse rate and duration were measured immediately before and after the procedure. No ill effect was seen on any of the units tested, pacemaker inhibition was not observed, and programmability was not affected. Metal detector security gates have no effect on implanted permanent pacemakers.