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J N Fox

Publications and source records attributed to J N Fox.

At least 19 recordsLinked to original sources

Comparison of the short-term biological effects of 7alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (Faslodex) versus tamoxifen in postmenopausal women with primary breast cancer.

7Alpha-[9-(4,4,5,5,5-pentafluoropentylsulfinyl)-nonyl]estra-1,3,5, (10)-triene-3,17beta-diol (ICI 182,780; Faslodex) is a novel steroidal antiestrogen. This partially blind, randomized, multicenter study compared the effects of single doses of long-acting ICI 182,780 with tamoxifen or placebo on estrogen receptor (ERalpha) and progesterone receptor (PgR) content, Ki67 proliferation-associated antigen labeling index (Ki67LI), and the apoptotic index in the primary breast tumors of postmenopausal women. Previously untreated patients (stages T(1)-T(3); ER-positive or -unknown) were randomized and received a single i.m. dose of ICI 182,780 50 mg (n = 39), ICI 182,780 125 mg (n = 38), or ICI 182,780 250 mg (n = 44) or oral tamoxifen 20 mg daily (n = 36) or matching tamoxifen placebo (n = 43) for 14-21 days before tumor resection surgery with curative intent. The ER and PgR H-scores, together with the Ki67LI were determined immunohistochemically in the matched pretreatment biopsy and the posttreatment surgical specimens. The apoptotic index was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling on the same samples. The effects of treatment on each of these parameters were compared using analysis of covariance. ICI 182,780 produced dose-dependent reductions in ER and PgR H-scores and in the Ki67LI. The reductions in ER expression were statistically significant at all doses of ICI 182,780 compared with placebo (ICI 182,780 50 mg, P = 0.026; 125 mg, P = 0.006; 250 mg, P = 0.0001), and for ICI 182,780 250 mg compared with tamoxifen (P = 0.024). For PgR H-score, there were statistically significant reductions after treatment with ICI 182,780 125 mg (P = 0.003) and 250 mg (P = 0.0002) compared with placebo. In contrast, tamoxifen produced a significant increase in the PgR H-score relative to placebo, and consequently, all doses of ICI 182,780 produced PgR values that were significantly lower than those in the tamoxifen-treated group. All doses of ICI 182,780 significantly reduced Ki67LI values compared with placebo (ICI 182,780 50 mg, P = 0.046; 125 mg, P = 0.001; 250 mg, P = 0.0002), but there were no significant differences between any doses of ICI 182,780 and tamoxifen. ICI 182,780 did not alter the apoptotic index when compared with either placebo or tamoxifen. Short-term exposure to ICI 182,780 reduces the ERalpha in breast tumor cells in a dose-dependent manner by down-regulating ER protein concentration. The reductions in tumor PgR content by ICI 182,780 demonstrate that ICI 182,780, unlike tamoxifen, is devoid of estrogen-agonist activity. Reductions in tumor cell proliferative activity (as indicated by Ki67LI) show that ICI 182,780 is likely to have antitumor activity in the clinical setting.

Aged↗

Evaluation of response to neoadjuvant chemoradiotherapy for locally advanced breast cancer with dynamic contrast-enhanced MRI of the breast.

AIMS: This study aimed to examine the feasibility of utilizing dynamic contrast-enhanced MRI (DCE-MRI) of the breast for the planning of surgical intervention following neoadjuvant therapy for locally advanced breast cancer (LABC). METHODS: Following their neoadjuvant therapy, women with LABC were followed-up by DCE-MRI in addition to clinical examination and mammography. If any modality suggested residual disease, surgery was carried out--initially salvage mastectomy and then breast-conserving surgery where appropriate. RESULTS: Seventeen women were recruited: stage III (n=16), stage IV (n=1) mean age 55 (range 34-74). Following neoadjuvant therapy, 10 mastectomies and two local excisions were performed for 10 histologically confirmed residual cancers. Median follow-up for those women not undergoing surgery is 3.24 (IQR 2.8-3.5) years. DCE-MRI proved 100% accurate for the delineation of residual disease and facilitated the planning of the local excisions. Clinical examination and mammography proved inaccurate (PPV 83% and 75% and NPV 55% and 80%, respectively). CONCLUSIONS: DCE-MRI is a potentially accurate method of delineating residual tumour following neoadjuvant therapy for LABC and may be used to plan appropriate operative intervention where required.

Adult↗

Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status.

PURPOSE: Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. In breast cancer, tumor VEGF has been shown to have a good correlation with relapse-free survival. The aim of this study was to determine the relation of serum VEGF levels to the various indices of breast cancer and known tumor markers carcinoembryonic antigen and CA15.3. EXPERIMENTAL DESIGN: Preoperative serum VEGF levels were determined in 200 women with breast cancer and compared with serum VEGF levels in 88 healthy female controls. RESULTS: The serum VEGF levels of the cancer patients as a group were significantly elevated compared with those of the controls (P < 0.0005). VEGF levels were elevated in patients with invasive cancer of ductal/no specific type, ductal carcinoma in situ, and estrogen receptor (ER)-positive tumors. Patients with lobular carcinoma and ER-negative tumors had serum VEGF levels comparable with those in the controls. VEGF was more sensitive than CA15.3 and carcinoembryonic antigen in detecting breast cancer. CONCLUSIONS: Preoperative serum VEGF detects breast cancer with a sensitivity of 62.1%. The relationship to cancer type and ER status may have future therapeutic implications. Additional long-term studies are required to determine the prognostic significance of serum VEGF.

Breast Neoplasms↗

Coexpression of estrogen receptor alpha and beta: poor prognostic factors in human breast cancer?

The cloning of a second estrogen receptor (ER), ER beta, has prompted a reevaluation of the role of ERs in breast cancer. The aim of this study was to determine the expression of both ER isoforms in normal (n = 23) and malignant (n = 60) human breast tissue by reverse transcription-PCR and correlate this information with known prognostic factors including tumor grade and node status. In normal breast tissue, expression of ER beta predominated, with 22% of samples exclusively expressing ER beta; this was not observed in any of the breast tumor samples investigated. Most breast tumors expressed ER alpha, either alone or in combination with ER beta. Interestingly, those tumors that coexpressed ER alpha and ER beta were node positive (P = 0.02; Fisher's exact test) and tended to be of higher grade. Because antiestrogens are agonists when signaling through the AP1 element, overexpression of ER beta in tumors expressing both ER subtypes may explain the failure of antiestrogen therapy in some breast cancer patients. Thus, ER beta may be a useful prognostic factor in patients with breast cancer.

Adult↗

Dynamic contrast enhanced magnetic resonance imaging of the breast is superior to triple assessment for the pre-operative detection of multifocal breast cancer.

BACKGROUND: Inadequately treated multifocal and multicentric disease results in increased local recurrence following breast-conserving surgery. The accurate preoperative diagnosis of multifocal/ centric breast cancer would facilitate the planning of appropriate surgery and prevent reoperation for residual disease. While triple assessment remains the established diagnostic technique, its sensitivity for the diagnosis of multifocal disease remains poor. Dynamic contrast enhanced Magnetic Resonance Imaging (DCE-MRI) of the breast represents an alternative emerging diagnostic modality that has been shown to be highly sensitive for the delineation of primary breast cancer. The aim of this study was to prospectively compare the diagnostic accuracy of DCE-MRI of the breast with conventional triple assessment for the preoperative diagnosis of multifocal/centric breast cancer. METHODS: Patients were recruited from the symptomatic breast clinics. All patients underwent standard triple assessment and DCE-MRI. The MRI scans were reported by a single radiologist blinded to the results of the triple assessment. Surgery was then planned accordingly to all available scan results and the specimens examined by a single pathologist. All patients who did not undergo surgery have been followed up for a minimum of 18 months. RESULTS: A total of 334 women were recruited. There were 178 (52%) cancers that were histologically confirmed and multifocal/centric breast cancer was diagnosed provisionally by the preoperative investigations in 68 (38%); multifocal n = 33, multicentric n = 35, of these patients. In this group, subsequent histology confirmed multifocal/centric disease in 50 (73.5%): multifocal n = 15, multicentric n = 35. Unifocal cancer was found in 15 (22%) and benign disease in 3 (4.4%). The resultant sensitivity, specificity, positive, and negative predictive values were 18%, 100%, 100%, and 76% for triple assessment and 100%, 86%, 73%, and 100% for DCE-MRI. CONCLUSION: DCE-MRI identified a subgroup of breast cancer patients with multifocal/centric disease not evident on standard triple assessment. MRI of the breast should be considered for the preoperative planning of surgery for primary breast cancer.

Aged↗

Prospective comparison of standard triple assessment and dynamic magnetic resonance imaging of the breast for the evaluation of symptomatic breast lesions.

OBJECTIVE: To compare the sensitivity and specificity of the traditional triple assessment of symptomatic breast lesions with contrast-enhanced dynamic magnetic resonance imaging. BACKGROUND: Although triple assessment is currently the gold standard for the assessment of symptomatic breast disease, its specificity is such that open biopsies are still required in many cases to be confident of the diagnosis. Contrast-enhanced dynamic magnetic resonance imaging of the breast represents an alternative diagnostic modality. METHODS: Patients were recruited from the symptomatic breast clinics. If any of the diagnostic modalities suggested malignancy, the lesion was excised. The remaining patients were followed clinically and radiologically. RESULTS: Two hundred eighty-five patients with a mean age of 43 years (range 21 to 77) were recruited. Malignant lesions were excised in 131 patients and benign lesions in 55 patients. The 99 patients who did not undergo surgery were followed clinically and radiologically for a median of 20 months. The sensitivity of each modality was as follows: clinical examination 84%, mammography 87.6%, fine-needle aspiration cytology 79.1%, triple assessment 99.2%, and magnetic resonance imaging 99.2%. In addition, histologically confirmed multifocal disease was detected in 40 patients on magnetic resonance imaging but in only 9 (22.5%) on mammography. The specificity for the diagnosis of benign disease was as follows: clinical examination 83.1%, ultrasound 88.9%, mammography 86.4%, fine-needle aspiration cytology 97%, triple assessment 59.1%, and magnetic resonance imaging 90.9%. CONCLUSION: Contrast-enhanced dynamic magnetic resonance imaging of the breast is as sensitive and more specific than the combined traditional triple assessment for the diagnosis of malignant breast lesions.

Adult↗

Interactive multimedia information program for use by breast-care nurses--a patient acceptability study.

AIMS: To design an interactive multimedia program for use by breast-care nurses and evaluate the acceptability of this technology to patients in the clinical setting. METHODS: In order to ensure that the clarity of the information was maintained the multimedia program was developed by a multidisciplinary team, including non-medical personnel and patients. A prospective analysis of the subjective impressions of patients with symptomatic breast disorders and breast-care nurses to a multimedia patient information system was then performed using a standard questionnaire and semi-structured interviews. RESULTS: Fifty women were recruited for the study. Thirty-six (72%) considered the multimedia counselling to be superior to the traditional modalities. Forty-nine (98%) graded the system as good or better. No patient regarded the technology as anxiety-provoking or inferior to the traditional leaflet-based approach. Women over 55 years old found the system as acceptable and easy to use as the younger women. CONCLUSIONS: The multimedia breast counselling programme was acceptable to patients and was considered superior to the traditional leaflet-based approach by the majority. The inherent advantages of this technology will lead to its increasing utilization in the clinical setting.

Adult↗

Vascular endothelial growth factor in premenopausal women--indicator of the best time for breast cancer surgery?

Timing of surgery in premenopausal patients with breast cancer remains controversial. Angiogenesis is essential for tumour growth and vascular endothelial growth factor (VEGF) is one of the most potent angiogenic cytokines. We aimed to determine whether the study of VEGF in relation to the menstrual cycle could help further the understanding of this issue of surgical intervention. Fourteen premenopausal women were recruited, along with three post-menopausal women, a woman on an oral contraceptive pill and a single male subject. Between eight and 11 samples were taken per person, over one menstrual cycle (over 1 month in the five controls) and analysed for sex hormones and VEGF165. Serum VEGF was significantly lower in the luteal phase and showed a significant negative correlation with progesterone in all 14 premenopausal women. No inter-sample variations of VEGF were noted in the controls. Serum from both phases of the cycle from one subject was added to MCF-7 breast cancer cells; VEGF expression in the supernatant was lower in the cells to which the luteal phase serum was added. The lowering of a potent angiogenic cytokine in the luteal phase suggests a possible decreased potential for micrometastasis establishment in that phase. This fall in VEGF may be an effect of progesterone and should be the focus of future studies.

Analysis of Variance↗

Short-term primary culture of epithelial cells derived from human breast tumours.

As experimental models for breast cancer, most studies rely on established human breast cancer cell lines. However, many of these lines were established over 20 years ago, many from pleural effusions rather than the primary tumour, so the validity of using them as representative models is questionable. This paper describes our experiences, over a 3-year period, in establishing short-term epithelial-cell-enriched preparations from primary breast tumours based on differential centrifugation followed by culture in selective media. Epithelial cells were successfully cultured from 55% of samples, but culture success did not appear to be correlated with tumour histology, stage, grade or node status. Epithelial cell-enriched cultures were immunopositive for broad-spectrum cytokeratin and epithelial membrane antigen (EMA). Positivity for keratin 19 confirmed that the cultures contained tumour-derived cells, which additionally showed significantly higher activity of the reductive pathway of the steroid-converting enzyme 17beta-hydroxysteroid dehydrogenase type I. That the cultures contained tumour and not normal epithelial cells was further substantiated by the complete absence of the calmodulin-like gene NB-1 in tumour-derived cultures; this is only associated with normal breast epithelia. Eighty-five per cent of cultures established from oestrogen receptor (ER)-positive tumours expressed ER in vitro; this was functional in 66% of cultures, although ER-positive phenotype was gradually lost over time. In conclusion, epithelial cells can be isolated and maintained as short-term cultures from primary breast tumours irrespective of histopathological or clinical details, providing a model system with a greater biological and clinical relevance than breast cancer cell lines.

17-Hydroxysteroid Dehydrogenases↗

Dynamic MR imaging of the breast combined with analysis of contrast agent kinetics in the differentiation of primary breast tumours.

OBJECTIVE: To assess dynamic Gd-DTPA-enhanced magnetic resonance (MR) imaging in the diagnosis of primary breast pathology, and to test the hypothesis that analysis of contrast agent kinetics increases specificity. METHODS: Forty-seven women underwent breast MR imaging using three-dimensional and dynamic spoiled gradient-recalled sequences. Image interpretation was based on the evaluation of lesion conspicuity, signal intensity, contour and enhancement pattern from the static acquisitions. Assessment of contrast kinetics was based on pixel-by-pixel analysis of the dynamic data. A two-compartment model described by three parameters (amplitude of uptake, exchange rate and washout rate), and a three-compartment model described by two parameters (permeability and exchange rate) were used. Regions of interest were drawn for all lesions found in the dynamic sections. Mean regional pixel values were calculated for each parameter and tested for diagnostic efficacy. RESULTS: Twenty-two malignant and 36 benign lesions were examined. Fibroadenomas accounted for 86% of the benign tumours. Image interpretation had a sensitivity of 0.95 and specificity of 0.86. The fat-suppressed post-contrast images permitted good visualization of the contour and matrix characteristics of fibroadenomas, but all non-fibroadenomatous benign lesions were classified as indeterminate or suspicious. Significant differences were found between benign and malignant lesions in the amplitude of uptake (P = 0.0008) and exchange rate (P < 0.00005) of the two-compartment model, and permeability (P=0.0001) and exchange rate (P < 0.00005) of the three-compartment model. However, image interpretation was superior to the isolated use of quantitative indices (P=0.02). The most discriminating parameters were the exchange rates of both models, with no significant difference between them. CONCLUSION: Assessment of lesion morphology is essential and probably sufficient for the differentiation of fibroadenomas from malignant tumours. However, specificity of conventional MR imaging may be much lower for other types of primary benign breast pathology. Analysis of Gd-DTPA kinetics improves the specificity obtained using simple enhancement measurements and can be used to produce parametric images that provide information about lesion heterogeneity, permeability and vascularity.

Adult↗

Conservative management of infective mastitis and breast abscesses after ultrasonographic assessment.

Current practice in this unit for a suspected breast abscess is preliminary ultrasonographic scan, aspiration of any pus, antibiotic therapy and repeat aspiration in the outpatient clinic if necessary. Inflammatory masses are treated with antibiotics alone. A retrospective review of this strategy has been made. Over a 2-year interval 53 patients were admitted to hospital with a suspected breast abscess. Twenty-two abscesses were aspirated, of which 19 resolved and three required subsequent incision and drainage. Eight patients underwent primary incision and drainage, one of whom required a second drainage procedure. In five patients the abscess discharged spontaneously before intervention. The remaining 18 patients were found on ultrasonography to have inflammation without evidence of focal pus which settled with antibiotic therapy in all but two patients. One of these was found to have an inflammatory cancer and the other developed an abscess, which was drained. Aspiration combined with ultrasonographic imaging is an effective alternative to incision and drainage.

Abscess↗

Dynamic gradient-echo and fat-suppressed spin-echo contrast-enhanced MRI of the breast.

PURPOSE: To evaluate heavily T2-weighted, dynamic contrast-enhanced and fat-suppressed magnetic resonance imaging (MRI) of the breast in comparison with conventional imaging and fine needle aspiration cytology (FNAC). PATIENTS AND METHODS: Fifty patients with surgically/pathologically proven breast disease were examined pre-operatively by MRI. The majority, 45 patients, had invasive carcinoma. T1-weighted spin-echo, T2-weighted fast spin-echo (with chemical-shift-selective fat-suppression in 20 cases), rapid dynamic contrast-enhanced gradient-echo and post-contrast fat-suppressed T1-weighted images were obtained. Signal intensity changes during dynamic scanning were assessed qualitatively and quantitatively. Comparison was made with the results of X-ray mammography, ultrasound and fine needle aspiration cytology. RESULTS: Unenhanced MRI was inadequate for determining the location, extent or nature of most lesions even when fat-suppressed T2-weighted images were obtained. Following contrast injection, there was significantly greater enhancement of invasive carcinomas than normal parenchyma. Invasive carcinomas of ductal and lobular subtypes did not differ significantly in their enhancement profiles. Prominent enhancement of the lesion periphery, which was a feature in 33 out of 50 cases (the majority of which were invasive carcinomas) was not due to central tumour necrosis. In four cases, invasive carcinomas which were clearly visible on early dynamic scans could not be identified on post-contrast fat-suppressed images. Lesions that were more numerous or extensive than had been recognised clinically or mammographically were revealed by MRI in 14 patients, though MRI was no more specific than conventional assessment. Invasion of the chest wall was accurately predicted by MRI in three cases. There was excellent correlation between tumour size shown by MRI and histopathology. FNAC was accurate in predicting the final histological diagnosis except in those cases where samples were unsatisfactory. CONCLUSIONS: Contrast-enhanced MRI appears useful in the assessment of suspected malignant breast masses, especially in younger women with predominantly glandular breast tissue. Specificity is no better than FNAC but tumour extent and multifocality are more accurately disclosed than by conventional imaging techniques. Contrast-enhanced chemical-shift-selective fat-suppressed images are sub-optimal in a small proportion of cases (particularly where lesions are located posteriorly) and some benign breast disease may appear misleadingly conspicuous on such images. Morphological features and quantification of lesion enhancement during dynamic scanning presently offer only limited prospects for discrimination between various pathologies. Heavily T2-weighted sequences appear of marginal value.

Adolescent↗

Dynamic contrast-enhanced magnetic resonance imaging of the breast combined with pharmacokinetic analysis of gadolinium-DTPA uptake in the diagnosis of local recurrence of early stage breast carcinoma.

RATIONALE AND OBJECTIVES: This study was designed to assess the efficacy of dynamic contrast-enhanced magnetic resonance imaging (MRI) of the breast combined with pharmacokinetic analysis of gadolinium (Gd)-DTPA uptake in the diagnosis of local recurrence of early stage breast carcinoma. METHODS: Fifty women treated with breast-conserving surgery and radiotherapy underwent breast MRI. Dynamic magnetic resonance data obtained at four preselected slice locations were analyzed to examine Gd-DTPA uptake based on a pharmacokinetic model using three parameters: wash-in rate, wash-out rate, and amplitude of uptake. Synthetic images were produced from the above parameters and their derivatives--maximum uptake and reciprocal of half the time to maximum. For each region of interest (ROI), median parameter values were calculated. The mean pixel signal intensity of each ROI was plotted against time, and an enhancement index was determined. RESULTS: Sixty ROIs were selected: 49 lesions were benign, and 11, malignant. Significant differences between benign and malignant lesions were found for the enhancement index (P < 0.0001), maximum uptake (P < 0.0001), amplitude of uptake (P < 0.0001), wash-in rate (P = 0.03), wash-out rate (P = 0.01), and the reciprocal of half the time to maximum (P = 0.0005). The respective sensitivities and specificities were as follows: for the enhancement index, 1.00 and 0.96; for maximum uptake, 1.00 and 0.96; for amplitude of uptake, 0.91 and 0.94; for wash-in rate 0.82 and 0.47; for wash-out rate 0.91 and 0.59; and for the reciprocal of half the time to maximum, 1.00 and 0.51. CONCLUSIONS: Dynamic scanning proved essential for the detection and differential diagnosis of local tumor recurrence. Pharmacokinetic analysis of Gd-DTPA uptake can be used to produce parametric images that retain the spatial resolution of the original images while providing additional information about lesion permeability and vascularity, and helping to avoid the observer variability associated with ROI analysis.

Adult↗

Dynamic contrast-enhanced and fat suppressed magnetic resonance imaging in suspected recurrent carcinoma of the breast: preliminary experience.

20 women with suspected recurrent breast cancer who had undergone previous breast-conserving operations were investigated using dynamic contrast-enhanced gradient echo (GRE) and fat suppressed spin echo (SE) magnetic resonance (MR) imaging. Histologically confirmed recurrent tumour was readily recognized on dynamic GRE scans by virtue of rapid, early and avid enhancement. Benign scars enhanced more slowly and reached lower magnitudes of enhancement. Fat suppressed SE images, which were typically acquired 10 min after contrast administration, were sensitive for the detection of tumour recurrence but lacked specificity. Early scanning after contrast administration offers the best prospects for distinguishing tumour recurrence from benign scarring. The criteria used to distinguish these two entities are highly dependent on the scan technique and the time at which images are obtained post-contrast.

Aged↗

Results of the first year of breast cancer screening in a district hospital.

The Humberside Breast Screening Service completed 1 year of screening by October 1990; 16,534 women were invited of whom 12,832 (77.6 per cent) attended. A group of 644 women (5.0 per cent) were called for further assessment and of these 134 underwent 135 primary surgical procedures. After assessment 25 were shown before operation to have cancer. One hundred and nine women had suspicious lesions and proceeded to surgical biopsy; 50 lesions proved malignant (benign: malignant biopsy ratio 1.2:1). The 75 malignant lesions represented a prevalence of 5.8 per 1000 of the screened population. Invasive cancer > 1 cm in diameter formed almost half of the malignant lesions. This service has cost 32 pounds per woman screened or 5533 pounds per cancer detected. The results are comparable to those of previous studies and suggest that a mammographic screening service can be successfully provided in a district hospital setting.

Biopsy, Needle↗

Drug-induced pemphigus related to angiotensin-converting enzyme inhibitors.

We report a case of drug-induced pemphigus caused by an angiotensin-converting enzyme inhibitor, captopril. The cutaneous reaction remitted after withdrawal of captopril therapy. Unique to this case, however, was the substitution of another angiotensin-converting enzyme inhibitor, enalapril, without exacerbation of the pemphigus. To the best of our knowledge, this is the first reported patient with captopril-induced pemphigus in whom no new lesions developed after subsequent treatment with enalapril. A difference in chemical structure between these two drugs, particularly of a sulfur moiety, may help explain why the drug-induced disease did not recur.

Aged↗

The hard penile circumferential fold as the presenting finding in primary syphilis: report of six cases.

BACKGROUND: Six patients with firm circumferential folds located in the balanic sulcus of the penis were studied. OBJECTIVE: The purpose of the study was to determine the origin of the lesions. METHODS: These patients were examined clinically, with dark-field examination when possible and with a serologic test for syphilis. RESULTS: All patients had reactive serologic tests for syphilis and had enlarged, firm, nontender, inguinal lymph nodes. CONCLUSION: Although we were unable to prove with certainty that the origin of these folds was syphilitic, all patients had clinical and serologic findings that supported the diagnosis of primary syphilis.

Adult↗