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Biomedical subjects

J Bornstein

Publications and source records attributed to J Bornstein.

At least 19 recordsLinked to original sources

Role of alpha(2)-adrenoceptors in the sympathetic inhibition of motility reflexes of guinea-pig ileum.

1. Sympathetic regulation of the motility of guinea-pig ileum was investigated using mesenteric nerve (MN) stimulation to inhibit motility reflexes, in vitro. 2. Transmural electrical stimulation (5 Hz, 1 s) in intact intestinal segments, or inflation of a balloon against the mucosa in opened segments, evoked contractions of the circular and longitudinal muscles oral to the stimulus. 3. MN stimulation (10 Hz, 5 s) usually abolished contractions of the longitudinal and circular muscles evoked by either electrical or mechanical stimuli. 4. The inhibition was mimicked by UK14,304 (70-100 nM) and abolished by idazoxan (100 nM), revealing an enhancement of circular muscle contractions. There was no evidence for alpha(2)-receptors on the muscle, suggesting sympathetic inhibition was via the myenteric plexus. 5. Possible sites of action of noradrenaline released from sympathetic nerves were investigated using intracellular recordings from the circular muscle in a multichambered organ bath. 6. When in the stimulation chamber, UK14,304 depressed (by 50 %) excitatory junction potentials (EJPs) recorded oral to a distension stimulus, but did not affect inhibitory junction potentials (IJPs) recorded anal to the stimulus. When added to a chamber between the stimulus and recording chambers, UK14,304 depressed EJPs by 40 %, but did not alter IJPs. When in the recording chamber, UK14,304 depressed EJPs by 20 %, but had no effect on IJPs. IJPs were inhibited, however, when UK14,304 was applied to the whole bath. 7. It is concluded that sympathetic activity inhibits intestinal motility mainly via alpha(2)-adrenoceptors on ascending interneurons and intrinsic sensory neurons of the orally directed reflex pathway.

Adrenergic alpha-Agonists↗

"Primary" versus "secondary" vulvar vestibulitis: one disease, two variants.

OBJECTIVE: Our aim was to determine whether women with primary vestibulitis-since the first episode of sexual intercourse-differ in disease characteristics and outcome of operative treatment from women with secondary vestibulitis. STUDY DESIGN: A total of 111 patients with severe vulvar vestibulitis underwent perineoplasty from 1991 to 1995. Thirty-nine (35%) of them had primary vestibulitis (ie, dyspareunia from the first attempt at sexual intercourse). They were compared with 72 (65%) who had secondary vestibulitis with regard to demographic, social, and medical variables, the presence of human papillomavirus deoxyribonucleic acid, physical and histopathologic findings in the vestibule, and surgical outcome. RESULTS: Women with primary vestibulitis were 5 years younger than those who had secondary vestibulitis (22.9 +/- 2.9 years vs 27.7 +/- 8.6 years, respectively; P <.0001) and differed in their marital status (unmarried, 84% vs 56%, respectively; P <.008), parity (nulliparous, 97% vs 67%, respectively; P <.0002), and involvement of the whole vestibule (74% vs 93%, respectively; P <.006). The 2 groups were similar in all other variables, including use of oral contraception, smoking, presence of human papillomavirus, dysuria, success of perineoplasty (average, 83%), and histopathologic findings. CONCLUSIONS: Women with primary vestibulitis were younger than women with secondary vestibulitis. Most other differences were dependent on the different ages of the 2 groups. Primary and secondary vestibulitis may therefore be two presentations of the same disease.

Adolescent↗

The classic approach to diagnosis of vulvovaginitis: a critical analysis.

OBJECTIVE: To correlate the symptoms, signs and clinical diagnosis in women with vaginal discharge, based on the combined weight of the character of the vaginal discharge and bedside tests, with the laboratory diagnosis. METHODS: Women presenting consecutively to the women's health center with vaginal discharge were interviewed and examined for assessment of the quantity and color of the discharge. One drop of the material was then examined for pH and the whiff test was done; a wet mount in saline and in 10% KOH was examined microscopically. The clinical diagnosis was based on the results of these assessments. Gram stain and cultures of the discharge were sent to the microbiology laboratory. RESULTS: One hundred and fifty-three women with vaginal discharge with a clinical diagnosis of vulvovaginitis participated in the study. Fifty-five (35.9%) had normal flora and the other 98 (64.1%) had true infectious vulvovaginitis (kappa agreement = 18%). According to the laboratory, the principal infectious micro-organism causing the vulvovaginitis was Candida species. Candida infection was associated with pH levels of less than 4.5 (p < 0.0001, odds ratio = 4.74, 95% confidence interval: 2.35-9.5, positive predictive value 68.4%). The whiff test was positive in only a small percentage of bacterial vaginosis (BV) (p = not significant (NS)). Clue cells were documented in 53.3% of patients with a laboratory diagnosis of BV (p < 0.02, positive predictive value 26.7%). CONCLUSIONS: The current approach to the diagnosis of vulvovaginitis should be further studied. The classical and time-consuming assessments were shown not to be reliable diagnostic measures.

Animals↗

Combined colposcopy, loop conization, and laser vaporization reduces recurrent abnormal cytology and residual disease in cervical dysplasia.

OBJECTIVES: Loop electrosurgical excision of the transformation zone (LEETZ) was recently associated with relatively high failure rates. We evaluated whether the combination of LEETZ with laser vaporization is superior to LEETZ alone in reducing the rates of recurrent abnormal cytology and residual disease. METHODS: The study population included 426 women with histologic diagnosis of cervical intraepithelial neoplasia (CIN) 2-3, of whom 289 (study group) were treated by LEETZ followed by laser vaporization of the crater base and walls and 137 (control group) were treated by LEETZ alone. All women were followed scrupulously at regular intervals for recurrent abnormal cytology and residual disease. The mean follow-up periods were 43 and 59 months for the study and control groups, respectively. RESULTS: Both groups were derived from the same community and were similar in epidemiologic characteristics and disease severity. Although the incidence of positive surgical margins was similar in both groups (10.4 and 9.5% for the study and control groups, respectively), recurrent abnormal cytology (10.2% vs 5.5%, P = 0.07) and histologic residual disease (21.4% vs 0%, P = 0.05) were more frequent among women in the control group. This applied to women with both negative and positive surgical margins. Both study and control women with positive surgical margins, especially at the endocervix, were at higher risk for recurrence. CONCLUSION: The addition of laser vaporization to LEETZ may improve outcome of both women with positive margins and women with negative margins. Our results support conservative management for all treated women, regardless of cone margin status.

Adolescent↗

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.

Adolescent↗

Increased endometrial thickness in women with hypertension.

OBJECTIVE: We noticed an increase in endometrial thickness in women with hypertension who were treated with a combination of medications, including beta-blockers. The purpose of this study was to examine whether the endometrium of hypertensive women is thicker than that of healthy women and to determine whether endometrial thickening in hypertensive women is directly related to the antihypertensive beta-blocker treatment. STUDY DESIGN: We compared 3 groups of postmenopausal patients as follows: (1) women with a history of essential hypertension treated with a combination of medications, including beta-blockers; (2) women with a history of hypertension treated with a combination of medications that did not include beta-blockers; and (3) healthy women without hypertension. All patients were interviewed and examined, blood tests were performed, and endometrial thickness in the anterior-posterior diameter was measured by vaginal ultrasonography. Among the exclusion criteria were diabetes or an abnormal fasting blood glucose level, obesity, hormonal medication or replacement hormonal therapy during the previous 6 months, and a history of hormonal disturbances, infertility, or polycystic ovary syndrome. RESULTS: Of 45 hypertensive women enrolled in the study, 22 were treated with a beta-blocker combination medication and 23 were treated with other antihypertensive medications. They were compared with 25 healthy women. There was no statistically significant difference in endometrial thickness between women treated with medications, including beta-blockers, and those who were treated with other hypotensive agents. Twenty percent of women with hypertension and none of the healthy women had endometrium >5 mm thick (P <.017; odds ratio, 8.22; 95% confidence interval, 1.22-infinity). CONCLUSION: Twenty percent of hypertensive postmenopausal women were found to have increased endometrial thickness. However, we were unable to substantiate an association between the type of treatment administered, whether beta-blockers were included, and the increase in endometrial thickness.

Adrenergic beta-Antagonists↗

Pure versus complicated vulvar vestibulitis: a randomized trial of fluconazole treatment.

OBJECTIVE: To examine the effectiveness of a 6-month treatment consisting of a weekly oral dose of 150 mg fluconazole for women with vestibulitis, and to explore the causes of treatment failure. METHODS: Forty women with vestibulitis were randomized to either of two treatment groups. One group received a 6-month low oxalate diet with calcium citrate complement, as a placebo, and the second group the same diet and calcium citrate with the addition of a weekly oral tablet of 150 mg fluconazole. The women were examined 3 months after completing treatment, for response to therapy. RESULTS: The addition of intensive 6-month fluconazole treatment did not lead to an outcome better than that attained by maintaining a low oxalate diet with calcium citrate supplementation. The satisfactory response rate was 15 and 30%, respectively. The presence of 'complicated vestibulitis', candidiasis concomitant with vestibulitis, decreases the satisfactory response rate regardless of the type of treatment administered (odds ratio 19.9, 95% CI 1.6, 250). CONCLUSION: Prolonged oral fluconazole is an ineffective treatment of vestibulitis, whether pure or complicated by concomitant vulvovaginal candidiasis. The coexistence of candidiasis and vestibulitis - complicated vestibulitis - might represent a subset of vestibulitis that is resistant to the currently available medical therapy.

Antifungal Agents↗

Telomerase activity in HPV-associated vulvar vestibulitis.

OBJECTIVE: To find a possible correlation between telomerase activity, mean telomere length and human papillomavirus (HPV) presence and type in vulvar vestibulitis. STUDY DESIGN: Twenty-two tissues excised during surgery for the treatment of severe vulvar vestibulitis and nine control tissue samples were tested for telomerase activity, mean telomere length, and HPV presence and type. RESULTS: Thirty-six percent of the tissues from vestibulitis patients were infected with HPV, mainly type 16/18, and none of the control tissue samples showed presence of HPV DNA (P < .02). Telomerase activity was detected in all tissues harboring HPV DNA, whereas only 64% of tissues without HPV DNA exhibited telomerase activity (P < .02). The mean telomere length was unchanged as compared to control samples. CONCLUSION: Telomerase activity in vestibulitis may be increased as a result of HPV infection, suggesting that HPV infection may play a role in the etiology of some cases of vulvar vestibulitis.

Adult↗

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.

Female↗

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.

Adult↗

A report of a gastrinoma localized preoperatively by endoscopic ultrasound only and a review of the approach to imaging in Zollinger-Ellison syndrome.

The addition of somatostatin receptor scintigraphy and endoscopic ultrasound to the preoperative assessment of patients with Zollinger-Ellison syndrome has improved the ability to localize gastrinomas. We report a patient with Zollinger-Ellison syndrome with a gastrinoma localized preoperatively by endoscopic ultrasound only. We review the literature regarding the sensitivity of somatostatin receptor scintigraphy and endoscopic ultrasound and discuss the approach to imaging in Zollinger-Ellison syndrome.

Adult↗

Increased telomerase activity and decreased telomere length in genital condylomata acuminata.

Our objective was to find a possible correlation between telomerase activity, mean telomere length and human papillomavirus (HPV) presence and type in genital condylomata acuminata. Fifteen biopsies from women with genital condylomata acuminata and nine control tissue samples were tested for telomerase activity, mean telomere length, and HPV presence and type. All condylomata exhibited telomerase activity, compared to 78% of the control samples. The mean telomere length of condylomata was significantly (P<0.002) shorter compared to telomere length in control tissue samples. All condylomata lesions were infected with HPV types 6/11, and more than half had additional infection with HPV 16/18. Mixed HPV 6/11 with 16/18 infection correlated with shorter telomeres than presence of HPV 6/11 alone in the lesions (4.68 +/- 0.44 kb vs 4.97 +/- 0.57 kb). None of the control tissue samples showed presence of HPV DNA. Telomerase activity may be a marker of proliferation rather than malignancy, whereas the mean telomere length could better serve as a marker for the progression of HPV lesions toward malignancy.

Biopsy↗

Clobetasol dipropionate 0.05% versus testosterone propionate 2% topical application for severe vulvar lichen sclerosus.

OBJECTIVE: Our goal was to evaluate short-term (3 months) and long-term (1 year) treatment of vulvar lichen sclerosus, by comparing topical application of testosterone propionate 2% in petrolatum with the corticosteroid clobetasol dipropionate 0.05%. STUDY DESIGN: There were 20 women in each treatment group. The patients' symptoms and the gynecologist's examination findings were recorded before treatment, at 3 months, and at 1 year after initiation of therapy. RESULTS: The symptomatic (subjective) effect of clobetasol treatment was similar to that of testosterone at the 3-month follow-up (p < or = 0.34), although objectively the signs of lichen sclerosus had improved more in the clobetasol group (p < or = 0.033). Both symptoms and signs were significantly more improved in the clobetasol-treated group at the 1-year follow-up examination (p < or = 0.02). Seventy percent of women treated by testosterone discontinued treatment because of a lack of response, whereas only 10% of the women treated with clobetasol stopped the treatment for that reason (p < or = 0.00042). CONCLUSION: Clobetasol is more effective than testosterone in the treatment of women with lichen sclerosus, especially in the long term.

Administration, Topical↗

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.

Adult↗

Interferon-beta and -gamma, but not tumor necrosis factor-alpha, demonstrate immunoregulatory effects on carcinoma cell lines infected with human papillomavirus.

BACKGROUND: Mechanisms whereby cells infected with human papillomavirus (HPV) escape immune surveillance, ultimately leading to invasive cervical carcinoma, may involve changes in local cytokine production, loss of responsiveness to cytokines, and alterations in the expression of immune-regulatory molecules such as histocompatibility-related leukocyte antigen (HLA) Class 1 and 2 and ICAM-I. This study examined the separate and combined effects of immune-activating cytokines, interferon (IFN)-gamma, IFN-beta, and tumor necrosis factor (TNF)-alpha, on the expression of these molecules. METHODS: Membrane protein expression and cellular mRNA levels were analyzed in cervical carcinoma-derived cell lines, SiHa and CaSki (with low and high HPV16 copy number, respectively), after exposure to cytokines. RESULTS: Both cell lines demonstrated constitutive expression of HLA Class 1 but not HLA Class 2 membrane antigens. IFN-gamma and -beta induced changes in Class 1 mRNA levels but not in membrane molecule expression. IFN-gamma induced dose-dependent expression of Class 2 membrane and mRNA molecules in both cell lines (more pronounced in SiHa than in CaSki cells), which was antagonized by IFN-beta. Constitutive ICAM-I membrane expression was observed only on CaSki cells, although ICAM-I mRNA was expressed in both cell lines. IFN-gamma up-regulated the membrane expression of this molecule, whereas IFN-beta led to its suppression. Differential modulation of ICAM-I mRNA was observed in both cell lines. A lack of response to TNF-alpha was observed throughout the experiments. CONCLUSIONS: The findings of this study point to possible mechanisms leading to suppression of local immune response in the pathogenesis of HPV-associated neoplasia. They also emphasize the complexity of developing an efficient cytokine therapy for patients with premalignant cervical disease.

Adjuvants, Immunologic↗

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.

Adolescent↗

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.

Adolescent↗