Efficacy of a proximal occlusion catheter with reversal of flow in the prevention of embolic events during carotid artery stenting: an experimental analysis.

OBJECTIVE: The role of percutaneous angioplasty and stenting of carotid bifurcation lesions has been limited by its potential for producing embolic debris. We evaluated the efficacy of a proximal occlusion catheter (POC) in the prevention of embolic events during carotid artery stenting. In addition, pressure measurements relevant to the clinical application of this device were obtained from 10 patients undergoing carotid endarterectomy. METHODS: The POC is a guiding catheter with an occlusion balloon attached on the outside of the catheter at its distal end. Occlusion of the common carotid artery (CCA) was achieved by inflating the balloon while access to carotid bifurcation lesions was obtained through the inner lumen. The POC was inserted in the CCA of 10 dogs via the femoral artery. The side port of the POC was connected to a sheath placed in the femoral vein, thereby creating an external arteriovenous shunt. Ten artificial radiopaque particles simulating embolic particles and contrast agent were introduced in the CCA and monitored fluoroscopically. As a control, the same procedure was performed with a standard guiding catheter without an occlusion balloon. In 10 patients undergoing carotid endarterectomy, the internal carotid artery (ICA) and external carotid artery stump pressures and the pressure in the internal jugular vein were measured. RESULTS: Without the external arteriovenous shunt, in all animals there was prograde flow in the distal CCA despite CCA occlusion. This flow was derived from the thyroid artery. However, once the arteriovenous shunt was activated, reversal of flow in the distal CCA was achieved in each animal, and all the artificial particles were recovered from the side port of the POC. In the control group, each particle embolized to the brain (100%, P <.01). In the patients, the mean stump pressures in the ICA and external carotid artery and the jugular vein pressure were 51.8 +/- 14.2, 62.2 +/- 15.1, and 6.5 +/- 3.5 mm Hg, respectively. In each case, the jugular vein pressure was the lowest among the three. CONCLUSIONS: Obtaining proximal CCA control by inflating the POC does not sufficiently prevent embolization. However, reversal of flow in the ICA can always be created with the external shunt, which effectively prevents embolization. Thus, POC may markedly lower procedural stroke rates during carotid artery stenting. The ability of POC to prevent embolization before crossing the lesion with a guidewire may be an important advantage over other distal protection devices.

Does the endovascular repair of aortoiliac aneurysms pose a radiation safety hazard to vascular surgeons?

OBJECTIVES: Endovascular aortoiliac aneurysm (EAIA) repair uses substantial fluoroscopic guidance that requires considerable radiation exposure. Doses were determined for a team of three vascular surgeons performing 47 consecutive EAIA repairs over a 1-year period to determine whether this exposure constitutes a radiation hazard. METHODS: Twenty-nine surgeon-made aortounifemoral devices and 18 bifurcated devices were used. Three surgeons wore dosimeters (1) on the waist, under a lead apron; (2) on the waist, outside a lead apron; (3) on the collar; and (4) on the left ring finger. Dosimeters were also placed around the operating table and room to evaluate the patient, other personnel, and ambient doses. Exposures were compared with standards of the International Commission on Radiological Protection (ICRP). RESULTS: Total fluoroscopy time was 30.9 hours (1852 minutes; mean, 39.4 minutes per case). Yearly total effective body doses for all surgeons (under lead) were below the 20 mSv/y occupational exposure limit of the ICRP. Outside lead doses for two surgeons approximated recommended limits. Lead aprons attenuated 85% to 91% of the dose. Ring doses and calculated eye doses were within the ICRP exposure limits. Patient skin doses averaged 360 mSv per case (range, 120-860 mSv). The ambient (> 3 m from the source) operating room dose was 1.06 mSv/y. CONCLUSIONS: Although the total effective body doses under lead fell within established ICRP occupational exposure limits, they are not negligible. Because radiation exposure is cumulative and endovascular procedures are becoming more common, individuals performing these procedures must carefully monitor their exposure. Our results indicate that a team of surgeons can perform 386 hours of fluoroscopy per year or 587 EAIA repairs per year and remain within occupational exposure limits. Individuals who perform these procedures should actively monitor their effective doses and educate personnel in methods for reducing exposure.

Measuring resolution in the contrast domain: the small letter contrast test.

BACKGROUND: Recent evidence suggests that small letter contrast sensitivity (CS) is more sensitive than visual acuity (VA) to defocus, luminance, binocular enhancement, and visual differences among pilot trainees. It would be valuable to make this test available for general use. We developed a hard copy (letter chart) version called the Small Letter Contrast Test (SLCT) and evaluated its sensitivity and reliability in comparison to standard vision tests. METHODS: The SLCT has 14 lines of letters with 10 letters per line. The letters are of constant size (20/25 or 4/5 at 4 m), but vary in contrast by line in 0.1 log steps (0.01 log units per letter). Normal room illumination is used. The SLCT was evaluated in 16 subjects under various conditions (spherical and astigmatic blur, low luminance, 2 eyes vs. 1 eye) to determine test sensitivity and reliability, and in patients with clinical conditions. Scores were compared to those obtained with standard tests of VA (Bailey-Lovie) and CS (Pelli-Robson). RESULTS: SLCT scores were similar to previous measures, and retest reliability was one line. The SLCT was more sensitive than VA to spherical and astigmatic blur, low luminance, and vision with two eyes vs. one eye. Greater sensitivity of the SLCT endured despite correction for variability. The SLCT was more sensitive than standard tests to visual loss from early cataract, keratoconus, corneal infiltrates, edema, and amblyopia. CONCLUSIONS: The SLCT is a sensitive, adjunctive test, which complements existing measures of VA. It can reveal subtle visual deficits that may be undetected by standard clinical techniques. The SLCT should prove useful for monitoring vision in refractive surgery, corneal and macular edema, optic neuritis, and for selection and evaluation of candidates for occupations requiring unique visual abilities like aviation.

Association of an estrogen receptor variant with increased height in women.

There is an association between a B region allele (here called the B' allele) of the estrogen receptor (ER) and a history of spontaneous abortion in women with ER positive breast cancer, but no such association for women with ER negative tumors or women without breast cancer. In this study we compared the heights of women carrying the B and B' alleles. The B' allele was identified by polymerase chain reaction to amplify genomic DNA around the polymorphic region of the ER gene, followed by allele specific oligonucleotide hybridization. This analysis used DNA obtained from blood lymphocytes. Women carrying the B' allele were significantly taller than those carrying the wild type allele (B allele). Multiple linear regression also demonstrated that this association remained (p = 0.017), controlling for the effects of age and race. Since the B' ER allele results from a silent mutation, a second mutation, segregating with it, no doubt plays a role in producing the high incidence of spontaneous abortion we reported previously and the height difference we report here. This second mutation might lie within the estrogen receptor itself or within one of the genes nearby.

Optical defocus: differential effects on size and contrast letter recognition thresholds.

PURPOSE: To determine if optical defocus produces a greater reduction in visual acuity or small-letter contrast sensitivity. METHODS: Letter charts were used to measure visual acuity and small-letter contrast sensitivity (20/25 Snellen equivalent) as a function of optical defocus. Letter size (acuity) and contrast (contrast sensitivity) were varied in equal logarithmic steps to make the task the same for the two types of measurement. RESULTS: Both visual acuity and contrast sensitivity declined with optical defocus, but the effect was far greater in the contrast domain. However, measurement variability also was greater for contrast sensitivity. After correction for this variability, measurement in the contrast domain still proved to be a more sensitive (1.75x) index of optical defocus. CONCLUSIONS: Small-letter contrast sensitivity is a powerful technique for detecting subtle amounts of optical defocus. This adjunctive approach may be useful when there are small changes in resolution that are not detected by standard measures of visual acuity. Potential applications include evaluating the course of vision in refractive surgery, classification of cataracts, detection of corneal or macular edema, and detection of visual loss in the aging eye. Evaluation of candidates for occupations requiring unique visual abilities also may be enhanced by measuring resolution in the contrast domain.

Estrogen-receptor polymorphism, spontaneous-abortion, and breast-cancer risk.

In 1988 we identified a polymorphism in the estrogen receptor (ER) gene. The newly identified allele, called B', contains a silent mutation in codon 87, part of the receptor's B domain. Because of the association we previously reported of the B' allele, spontaneous abortion, and estrogen receptor positive breast cancer, we have now performed a preliminary case-control study to estimate the risk of breast cancer in women with the B' allele. Among BB' heterozygotes with ER-positive breast cancers (23 cases, 27 controls), the risk of this type of cancer was strongly related to a history of spontaneous abortion; the age-adjusted odds ratios were 4.1 (95% confidence limits, 0.95-18) after one spontaneous abortion and 9.7 (1.6-61) after two or more spontaneous abortions. No such association was seen for the risk of ER-negative breast cancer in BB' heterozygotes (N=18). Moreover, among BB homozygotes (137 cancer patients, 235 controls), spontaneous abortion was not related to an increased risk of breast cancer, either ER-positive or ER-negative. In BB' patients with ER-positive tumors, receptor concentrations were significantly lower in those who had a history of spontaneous abortion than in those without previous spontaneous abortions. These findings suggest involvement of a functional mutation associated with the B polymorphism, which is either elsewhere in the ER gene region or in a closely linked gene.

Estrogen receptor variant and hypertension in women.

Eighty-eight women visiting a gynecologist were tested for an estrogen receptor B-variant allele. The women were ethnically and racially homogeneous to a large degree. They were from a suburb of Long Island, and most were white. The 12% incidence of hypertension in women with the estrogen receptor wild-type allele is comparable to the 13-32% incidence in the general population of women aged 55-64 years. However, the 48% incidence of hypertension in women with the estrogen receptor B-variant allele is considerably higher than in the general population of women in this age group. We conclude that the presence of the estrogen receptor B-variant allele might have increased the prevalence of hypertension in the women in this study.

An estrogen receptor genetic polymorphism and a history of spontaneous abortion--correlation in women with estrogen receptor positive breast cancer but not in women with estrogen receptor negative breast cancer or in women without cancer.

We previously identified a polymorphism in the human estrogen receptor gene. In a preliminary study on women with estrogen receptor positive (ER+) breast tumors, we found that the presence of the rarer of the two alleles, the B' allele, is correlated with a history of spontaneous abortion. Because that study evaluated only women with estrogen receptor positive (ER+) breast cancer, it was unknown whether the observed correlation was restricted to the cancer group or was independent of breast cancer. We have now extended our analysis to include not only additional women with ER+ breast cancer, but also those with estrogen receptor negative (ER-) breast cancer and women without cancer. Results of the current study continue to show an association between the B' allele and a history of spontaneous abortion in the ER+ breast cancer group. There was no such correlation either in the ER- breast cancer group or in the group without cancer. Also, we continue to observe, in the ER+ breast cancer group, a significantly higher concentration of ER protein in tumors from homozygous wild type women (genotype BB), than in the tumors from women who are heterozygous for the rarer allele (genotype BB'). We conclude that the combination of spontaneous abortion and the BB' ER genotype may be a marker for breast cancer susceptibility.

Type IX Ehlers-Danlos syndrome: bladder diverticula with transitional cell carcinoma.

Patients with type IX Ehlers-Danlos syndrome have a tendency for development of diverticulae of the urinary bladder, and these often recur after surgical excision. We report on a patient with this syndrome in whom an extensively infiltrating transitional cell carcinoma developed in a diverticulum. To our knowledge, this is the first reported case of malignancy developing in a patient with type IX Ehlers-Danlos syndrome. The highly aggressive nature of the neoplasm is discussed in relation to the dampened desmoplastic response to the tumor, observed in this patient.

Incidence of an estrogen receptor polymorphism in breast cancer patients.

We previously identified a polymorphism in the human estrogen receptor (ER) gene, within the coding region for the protein's amino terminal B-domain. In estrogen receptor-positive (ER+) breast tumors, the variant allele was preferentially associated with lower levels of ER, and was clinically correlated with frequent spontaneous abortions. DNA sequencing revealed a point mutation that changes codon 86 from Ala to Val and a silent mutation in codon 87. Because we initially detected the variant allele by analyzing RNA, only those tissues in which the ER gene is actively expressed were suitable for genotype analysis. We now describe an assay that uses genomic DNA as the substrate for determining the ER B genotype, DNA containing the polymorphic region of the ER gene is amplified by the polymerase chain reaction, then the amplified DNA is hybridized with radiolabeled oligonucleotide probes complementary to the wild type and variant ER alleles. This method allowed us to determine the ER B genotype of women with ER+ and ER- tumors, starting with minute amounts of DNA from frozen or paraffin embedded tissues. ER B genotyping was also performed on women without breast cancer using DNA extracted from blood cells. The combined results from analyses of RNA and DNA from 300 breast cancer patients showed that 12% were heterozygotes. In the ER+ group (n = 183), 11.5% carried the variant gene compared to 12.8% in the ER-negative group (n = 117) (chi 2 = 0.11; df = 1; p greater than 0.25).(ABSTRACT TRUNCATED AT 250 WORDS)

Topical anesthesia for gynecologic procedures.

Topical benzocaine 20% gel was evaluated for its ability to reduce pain associated with several common gynecologic procedures. In the first phase of the investigation, designed to determine the efficacy of the gel, 40 women received it before one or more of five procedures (cervical biopsy, intrauterine device insertion, endocervical curettage, paracervical block, and tenaculum placement). These women reported significantly less pain than 42 control subjects (P less than .05 to P less than .0005). In the second phase of the study, a placebo gel was compared in a blind fashion with 20% benzocaine gel in 63 study subjects and 64 control women undergoing procedures similar to those in the first part of the study. The modal pain rating by both physician and patient was "none" in the study group for all procedures except endocervical curettage, for which the rating was "mild"; ratings were "mild" or "moderate" in the control group. Compliance with respect to keeping follow-up visits was significantly greater in the study group. These data indicate that benzocaine 20% significantly reduces the pain experienced by patients after many gynecologic procedures performed vaginally.