Challenging management of gingival squamous cell carcinoma: a 10 years single-center retrospective study on Northern-Italian patients.

BACKGROUND: Aim of this study was to describe the outcome of patients with gingival squamous cell carcinoma (GSCC), and to recognize aspects affecting clinical course and to consider survival rate. MATERIAL AND METHODS: The case records of patients, over a 10-year period, were retrospectively examined. Differences in distribution of the potential risk factors by prognosis were investigated through non-parametrical tests (Wilcoxon Rank-Sum and Fisher's Exact). Survival curves for age, therapy and stage were built by the Kaplan-Meier method and compared with Log-Rank test. RESULTS: 79 patients were analysed. Significant increase in mortality for patients older than 77 and for those with advanced stages was found. Cumulative survival rate 5 years after the diagnosis was 43%, while at 10 years was of 11%. CONCLUSIONS: With a statistical relationship between age and tumour stage with survival rates, and 70% of GSCC cases identified as stage IV, early GSCC diagnosis remains challenging.

Can atrophic-erosive oral lichen planus promote cardiovascular diseases? A population-based study.

OBJECTIVE: Lichen planus has been recently associated with an increased risk of cardiovascular diseases (CVDs). The oral manifestations can be divided into white hyperkeratotic lesions (WL) and atrophic and erosive lesions (RL). The aim of this report was to compare the presence of CVDs between patients affected by WL or RL, to test the hypothesis that RL are associated with an increased incidence of CVDs. SUBJECTS AND METHODS: Patients were analysed through a complete collection of all the risk factors for CVDs. The primary endpoint was the occurrence of a cardiovascular event-acute coronary syndrome (ACS), any revascularization or stroke/TIA. A multivariable logistic regression model, adjusted for age at diagnosis, body mass index, smoking, alcohol consumption, diabetes, hypertension, CVDs familiarity and periodontitis, was performed. RESULTS: A prospective cohort of 307 patients has been evaluated; 185 (60.3%) had WL and 122 RL (39.7%). Twenty-four patients had a CVD. ACS occurred more frequently in RL (adjusted odds ratio 5.83; 95% CI: 1.16-29.39), mainly due to the higher risk of it after the histological diagnosis of Oral lichen planus OLP (odds ratio 4.23; 95% CI: 0.66-27.23). CONCLUSION: Patients with RL could possibly have a higher risk of developing ACS. Further analysis on larger cohort is however warranted.

Randomized, placebo-controlled, double-blind trial of clobetasol propionate 0.05% in the treatment of oral lichen planus.

OBJECTIVE: To perform a randomized, placebo-controlled, double-blind study, with a follow-up period of 6 months, for the use of topical clobetasol in cases of symptomatic oral lichen planus (OLP). SUBJECTS AND METHODS: Thirty-two participants were analyzed, with the aims of: (I) to compare the usefulness of topically applied clobetasol propionate 0.05% (mixed with 4% hydroxyethyl cellulose gel) and 4% hydroxyethyl cellulose gel alone (considered as placebo) in the management of OLP; (II) to describe which of them is quicker in decreasing signs and reported symptoms, and (III) which is able to give the proper longer remission in the follow-up. RESULTS: Symptoms improved in all clobetasol-treated patients during the first 2 months of therapy, while only 50% of placebo control group (p = .005) displayed similar results; of the remaining half, 12.5% did experienced a worsening while 37.5% remained stable. Regarding clinical signs, 87.5% of clobetasol-treated patients improved, while only 62.5% of the placebo-treated patients had a positive response (p = .229). CONCLUSIONS: It is possible to report that clobetasol, at this dosage, has been more effective than a placebo at provoking symptoms improvement in subjects affected by atrophic-erosive oral lesions.

Describing the gingival involvement in a sample of 182 Italian predominantly oral mucous membrane pemphigoid patients: A retrospective series.

BACKGROUND: The oral cavity has been frequently described as the only site of involvement or as the first manifestation of mucous membrane pemphigoid (MMP), being the gingival tissues often involved, but usually this has been effusively detailed in limited case series. This is a retrospective evaluation of the gingival involvement in 182 Italian patients with oral MMP. MATERIAL AND METHODS: The diagnosis of MMP was established by both clinical morphology and direct immunofluorescence finding. Patient information (age, gender, risk factors and medical status) and parameters of manifestation (lesions' distribution, site and type) were detailed. RESULTS: The mean age was 62 years for women (n=137) and 67 years for men (n=45). Patients had several sites of oral involvement; the gingiva was the most common one, affecting 151 patients (82.96%; 119 f - 32 m). Female subjects had more possibilities to develop gingival lesions than male patients (P = 0.005). Sixty-five patients (35.7%; 58 f - 7 m) had pure gingival involvement. Patients with lower gingival involvement statistically had more complaints (P = 0.006). CONCLUSIONS: This report is one of the largest about predominantly oral MMP cases, detailing the very frequent gingival involvement; this could be crucial not only for oral medicine specialists but also for primary dental healthcare personnel and for periodontists.

A report on the clinical-pathological correlations of 788 gingival lesion.

BACKGROUND: The diagnosis and treatment of a variety of non-plaque related gingival diseases have become an integrated aspect of everyday dentistry. The aim of this study was to analyse the relationship between clinical appearance and histopathological features of gingival lesions in a large Northern Italian population. MATERIAL AND METHODS: A retrospective study of 788 cases of gingival and alveolar mucosal biopsies was set up. Statistical analysis was performed by calculating the odds ratio and 95% confidence interval (C.I.), in order to assess the degree of association between the clinical parameters considered (primary lesions) and the single pathologies, statistically evaluated by Mantel-Haenszel tests. The correlation between clinical and histological diagnosis was classified as follow: 1) expected data (ED): provisional clinical diagnosis; 2) real data (RD): final histopathology diagnosis; 3) concordant data (CD): correspondence between the expected data and real data. The correlation was calculated as follow: CC (complete concordance) = CD x 100 / ED, this expressing the percentage in which the clinical and the histological diagnosis overlapped. RESULTS: The most frequently observed and biopsied primary lesions resulted to be exophytic, followed by mucosal colour changes and finally by losses of substance. The statistically significant association between primary lesion and their manifestation in gingival pathologies was reported. Volume increases, for instance, were positively correlated to plasma cell epulis, pyogenic granuloma, fibrous reactive hyperplasia and hemangioma. Verrucous-papillary lesions were most often seen in verrucous carcinoma, verrucous leukoplakia and mild dysplasia. White lesion resulted to be related to leukoplakia or oral lichen planus. Red lesions resulted to be related only oral lichen planus. Erosive vesicle-bullous lesions were linked to disimmune pathologies. Ulcerative lesions were positively associated to oral squamous cell cancer. Finally, potentially malignant disorders have the most percentage high concordance. Among the malignant lesions, the correlation increased up to the squamous cell carcinoma and leukaemia. CONCLUSIONS: This article presented the frequency and the clinico-pathological concordance of all primary lesions and the histopathological diagnosis of gingival lesions. For every primary lesion, it is possible to correlate a specific histopathological diagnosis in a statistical manner. This can be a valuable aid for not specialist clinicians who daily observe mucosae and have the opportunity to intercept major diseases.

Favourably effective formulation of sodium iodide and salicylic acid plus professional hygiene in patients affected by desquamative gingivitis.

The aim of this prospective pilot study was to evaluate the efficiency of an oral hygiene protocol, in combination with a solution of sodium iodide associated to salicylic acid (SISA), in patients affected by desquamative gingivitis (DG). Twenty patients not totally responding to conventional topical therapies, were selected. They received oral hygiene instructions with non-surgical periodontal therapy in a 21-day cohort study (during 3 weekly appointments). The SISA was used at the end of each session, with an impregnated gauze (with 5 ml of the solution) applied for 15 minutes for the upper jaw, and for a further 15 minutes with a new gauze for the lower. Evaluated clinical outcome variables included the full mouth plaque (FMPS) and bleeding (FMBS) scores, probing depth, patient related outcome and clinical gingival signs. Two months after concluding the planned protocol, a statistically significant reduction was observed for FMPS (P=0.032), FMBS (P=0.038), reported pain (P=0.000) and gingival clinical improvement (P=0.005). Topical application of SISA and professional oral hygiene procedures are connected with improvement of gum status, and decrease of related pain in subjects affected by severe DG.

Pimecrolimus vs. tacrolimus for the topical treatment of unresponsive oral erosive lichen planus: a 8 week randomized double-blind controlled study.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease, affecting nearly 1-2% of the population; Proposed therapies are usually symptomatic and numerous drugs have been used, but recently, it has been published that there is insufficient evidence to support the effectiveness of any specific treatment as being superior. To the best of our knowledge, direct evaluation of the efficacy of topically applied pimecrolimus and tacrolimus in the treatment of atrophic-erosive OLP, refractory to topical steroids, is still lacking. OBJECTIVES: To assess the efficacy and safety of topical calcineurin inhibitors for unresponsive OLP. An 8 week randomized, double-blind controlled trial, followed by a 6 month follow-up period. Patients were treated with either pimecrolimus 1% cream or tacrolimus 0.1% ointment, both mixed with an equivalent amount of 4% hydroxyethyl cellulose gel. The medications were to be applied twice daily for 2 months. Each patient was examined at the beginning of therapy, and then every 2 weeks during the treatment and every 3 months of follow-up. Main outcome measures were: (i) to compare the effectiveness of topically applied pimecrolimus and tacrolimus; (ii) to evaluate which is more cost-effective; (iii) to determine which drug is faster in reducing signs and symptoms and (iv) which gives the longest remission. RESULTS: Thirty patients were involved in the study. Both drugs were effective at inducing clinical improvement, with no statistical difference. Pimecrolimus creams revealed a significantly better stability of the therapeutic effectiveness (P = 0.031). CONCLUSION: Both medications would currently appear to be a treatment of choice for patients with unresponsive atrophic-erosive OLP. Pimecrolimus seemed to be more effective in providing long-term resolution of signs and symptoms. Future efforts are however needed to obtain more objective evidence of the benefit of these medications in the treatment of immunologically mediated oral mucosal lesion.

Do changes in spheno-occipital synchondrosis after rapid maxillary expansion affect the maxillomandibular complex?

AIM: This was to evaluate changes in spheno-occipital synchondrosis one year after rapid maxillary expansion (RME), in order to assess the influence that any change might have on sagittal and vertical skeletal cephalometric variables. MATERIALS AND METHODS: Patients were selected consecutively and grouped into: Group 1 comprised 30 Caucasian patients (13 m; 17 f) undergoing RME therapy; after active expansion therapy, the Haas expander was worn as passive retainer for an average of 7 months. Group 2 as control included 14 untreated subjects (6 m, 8 f), matched by age, sex and vertebral skeletal maturity (CVM method, stages 1-3). Six cephalometric variables concerning spheno-occipital synchondrosis were studied: N-S-Ba; SOS-Ba; SOS-S; S-Ba; Ba-N; S-N; nine skeletal variables for sagittal and vertical evaluation were also checked. T-test was used for comparing the 2 groups data. RESULTS: A statistically-significant opening of the spheno-occipital synchondrosis and increase of the posterior cranial base length (Ba-SOS) were found between group 1 and 2. After 1 year, these modifications in spheno-occipital syncondrosis produced no change in the anteroposterior or vertical skeletal parameters examined. CONCLUSION: After RME there were statistically significant effects on spheno-occipital synchondrosis length and cranial base angle; however, these changes in the mid-term did not affect the vertical or sagittal parameters of the skeletal maxillomandibular complex.

Cancer in pregnancy: maternal and fetal implications on decision-making.

BACKGROUND: Cancer complicates one out of 1,000 pregnancies. No standardized therapeutic interventions have been reported for these patients. METHODS: Fifteen patients with cancer during pregnancy were diagnosed between 6.5 and 36 weeks of gestational age between January 1991 and December 2007. RESULTS: Among the 15 cases one patient with early diagnosis (11 weeks) asked for interruption of pregnancy, two patients rejected chemotherapy in order to avoid fetal effects, seven patients underwent surgery during the first or second trimester, and two patients agreed to start the treatment only after delivery. Standard platinum-based chemotherapy (cisDDP) was postponed in six patients to the second trimester (administered after surgery in 2 cases). Chemotherapy was started between 18.3 and 29.6 weeks (median 22.3 weeks). One patient had pPROM (22.3 weeks) after chemotherapy with cisDDP. Ten patients were delivered by elective cesarean section and three by vaginal delivery. Mean gestational age at delivery was 33.5 weeks (range 32.1-40.0); mean weight at birth was 2,550 g (range 1,250-3,450). None of the newborns showed congenital malformations, and all had normal Apgar scores. Anemia occurred in two newborns. At a median follow-up of 56 months (range 2-198 months) all children were well and healthy. Eleven out of 15 mothers are alive and well, and one is alive with disease. An advanced neoplasm was diagnosed in three patients who died. CONCLUSION: When platinum-based chemotherapy is administered during the 2nd-3rd trimester, adverse effects in newborns are comparable to those in the general population. Deliberate treatment delay to achieve fetal viability or to improve fetal outcome may be reasonable for patients with early-stage cancer.

Coronary flow reserve by transthoracic echocardiography predicts epicardial intimal thickening in cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is the leading cause of morbidity and mortality in heart transplantation (HT). We sought to investigate the role of coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) in CAV diagnosis. CAV was defined as maximal intimal thickness (MIT) assessed by intravascular ultrasound (IVUS) > or =0.5 mm. CFR was assessed in the left anterior descending coronary artery in 22 HT recipients at 6 +/- 4 years post-HT. CAV was diagnosed in 10 patients (group A), 12 had normal coronaries (group B). The mean MIT was 0.7 +/- 0.1 mm (range 0.03-1.8). MIT was higher in group A (1.16 +/- 0.3 mm vs. 0.34 +/- 0.07 mm, p < 0.0001). CFR was 3.1 +/- 0.8 in all patients and lower in group A (2.5 +/- 0.6 vs. 3.7 +/- 0.3, p < 0.0001). CFR was inversely related with MIT (r =-0.774, p < 0.0001). A cut point of < or =2.9, identified as optimal by receiver operating characteristics analysis was 100% specific and 80% sensitive (PPV = 100%, NPV = 89%, Accuracy = 91%). CFR assessment by CE-TTE is a novel noninvasive diagnostic tool in the detection of CAV defined as MIT > or =0.5 mm. CFR by CE-TTE may reduce the need for routine IVUS in HT.

The prognostic value of antenatal ultrasound in cases complicated by fetal ovarian cysts.

OBJECTIVE: Ovarian cysts are relatively common prenatal findings in female fetuses. The aim of this study is to evaluate the ability of antenatal ultrasound in predicting spontaneous regression or a need for surgery. DESIGN: All cases of fetal ovarian cysts treated in our Department between 2007 and 2016 were included. Patients underwent a sonographic monitoring in utero and after birth until spontaneous or surgical resolution. Subjects were divided into two groups according to their postnatal management. Receiver-operating characteristics (ROC) curves were used to test the predictive ability for postnatal surgery of the cyst's mean and maximum diameters; their optimal cut off points were also determined. RESULTS: 38 cases of antenatally-detected fetal ovarian cysts were included. 12/38 cases underwent surgery (Group A). 26/38 cases were resolved spontaneously (Group B). Cyst size of those which were surgically excised significantly differed from those that regressed spontaneously. ROC curve pointed to 45 mm and 47 mm as optimal cut off points for the mean and the maximum cystic diameters, respectively. CONCLUSIONS: Cyst size and echo-structure seemed good predictors for prognosis after birth. The optimal cut off points of the cysts mean and maximum diameters in predicting postnatal surgery have been identified as 45 mm and 47 mm, respectively.

Post-transplant lymphoproliferative disorders after heart or kidney transplantation at a single centre: presentation and response to treatment.

Post-transplant lymphoproliferative disorders (PTLD) is a serious complication after solid organ transplantation. Reduction of immunosuppression (RI) alone is not able to control the disease. We report a prospective analysis of 30 patients with PTLD after heart or kidney transplantation. Only 5 of 30 patients, treated solely with RI, obtained a complete response. Five patients were treated heterogeneously; in the remaining 20, the efficacy and safety of a weekly anthracycline-based chemotherapy were assessed. Sixteen patients obtained a complete remission. One death was related to treatment. With a median follow-up of 36 months, 3-year overall survival was 63.3% and 57% for the entire group and the chemotherapy-treated group, respectively. Moreover, 4 second neoplasms were observed in the chemotherapeutic group. In this study, we demonstrated that most PTLD need other treatment than RI and a weekly regimen is manageable and has a favourable impact on long-term survival.

Randomized trial in advanced ovarian cancer comparing cisplatin and carboplatin.

The aim of this multicenter randomized trial was to compare carboplatin (400 mg/m2) and cisplatin (100 mg/m2) in patients with untreated advanced epithelial ovarian cancer. Toxicity and treatment efficacy assessed by pathological response rate, progression-free survival, and survival were the endpoints of the study. One hundred seventy-three patients with advanced epithelial ovarian cancer, F.I.G.O. (International Federation of Gynecology and Obstetrics) stage III and IV were accrued in the trial. The median follow-up time was 15 months (maximum, 34); three patients in each treatment arm were not eligible (four, nonepithelial ovarian cancer type; one, no data, and one, stage II). Patient characteristics were similar in the two groups. In the carboplatin-treatment arm, the overall pathological response rate was 57.3% and the complete pathological response rate was 26.8%. In the cisplatin-treatment arm, the overall pathological response rate was 71.6% and the complete pathological response rate was 24.7%. There was no statistical difference in the two arms in survival or progression-free survival. Cisplatin was more nephrotoxic while carboplatin induced a higher degree of myelosuppression, especially thrombocytopenia; however, severe hematological toxicity was seldom observed. Carboplatin is a cisplatin analog with definite activity in ovarian cancer, but it is more active than the parent compound. Because of less nonhematological toxicity, carboplatin is undoubtedly a useful substitute in patients who cannot be given cisplatin. Further experience is needed to indicate whether or not carboplatin should completely displace cisplatin in the clinical treatment of ovarian cancer.

Increased myocardial GRP94 amounts during sustained atrial fibrillation: a protective response?

BACKGROUND: Structural and phenotypic changes of cardiomyocytes characterize atrial fibrillation. We investigated whether changes in the glucose-regulated protein GRP94, which is essential for cell viability, occur in the presence of chronic atrial fibrillation. METHODS AND RESULTS: Samples of fibrillating atrial myocardium obtained from both goat and human hearts were analyzed for GRP94 expression by an immunologic approach. In goats, atrial fibrillation was induced and maintained for 2, 4, 8, and 16 weeks. After 16 weeks of atrial fibrillation, cardioversion was applied and followed by 8 weeks of sinus rhythm. GRP94 levels doubled in goat atrial myocytes after 4 to 16 weeks of fibrillation with respect to normal atria and returned to control levels in atrial myocardium of cardioverted goats. Immunohistochemical analyses confirm that GRP94 increase occurred within cardiomyocytes. Significantly, increased levels of GRP94 were also observed in samples from human fibrillating atria. In the absence of signs of myocyte irreversible damage, the GRP94 increase in fibrillating atria is comparable to GRP94 levels observed in perinatal goat myocardium. However, calreticulin, another endoplasmic reticulum protein highly expressed in perinatal hearts, does not increase in fibrillating atria, whereas inducible HSP70, a cytoplasm stress protein that is expressed in perinatal goat hearts at levels comparable to those observed in the adult heart, shows a significant increase in chronic fibrillating atria. CONCLUSIONS: Our data demonstrate a large, reversible increase in GRP94 in fibrillating atrial myocytes, which may be related to the appearance of a protective phenotype.

Skin cancer in heart transplant recipients: risk factor analysis and relevance of immunosuppressive therapy.

BACKGROUND: The frequency of skin tumors of all types and specifically of squamous cell carcinoma (SCC) is increased in heart transplantation (HT), but the predisposing risk factors are controversial. METHODS AND RESULTS: We studied 300 patients (age 49+/-15 years, 258 men, mean follow-up 4.6 years, follow-up range 1 month to 12 years) who were receiving standard double (cyclosporin plus azathioprine) or triple (cyclosporin plus azathioprine plus prednisone) therapy. The first-year rejection score was calculated for endomyocardial biopsy samples (International Society for Heart and Lung Transplantation grade 0=0, 1A=1, 1B=2, 2=3, 3A=4, 3B=5, and 4=6) and used as an indirect marker of the level of immunosuppression. Multivariate analysis (Cox regression) included age at HT, sex, skin type, first-year rejection score, presence of warts and solar keratosis, lifetime sunlight exposure, and first-year cumulative dose of steroids. The incidence of skin tumors of all types increased from 15% after 5 years to 35% after 10 years after HT according to life-table analysis. Age at HT of >50 years (P:=0.03, RR=5.3), skin type II (P:=0.05, RR=2.6), rejection score of 19 (P:=0.003, RR=5.7), solar keratosis (P:=0.001, RR=6.9), and lifetime sunlight exposure of >30 000 hours (P:=0.0003, RR=7.6) were risk factors for SCC. CONCLUSIONS: Older age at HT, light skin type, solar keratosis, greater sunlight exposure, and high rejection score in the first year were independently associated with an increased risk of SCC. The progressive increase in cancer frequency during follow-up and the association with high rejection scores suggest that both the length and level of immunosuppression may be relevant. Because cumulative immunosuppressive load is cumbersome to calculate, a high rejection score in the first year may provide a useful predictor for patients at risk.

A phase I study of ifosfamide and doxorubicin with recombinant human granulocyte colony-stimulating factor in stage IV breast cancer.

Our objective was to define the maximum tolerated dose of an escalating dose of ifosfamide in combination with a fixed dose of doxorubicin supported by granulocyte colony-stimulating factor (Neupogen). Eighteen women with stage IV breast cancer were enrolled in a Phase I study of an escalating dose of ifosfamide (1.2 g/m2/day for 5 days-2.75 g/m2/day for 5 days) with doxorubicin 20 mg/m2/day for 3 days. Granulocyte colony-stimulating factor was used at 5 microgram/kg on day 6 until hematological recovery. Prophylactic antibiotics were also used. The maximum tolerated dose of ifosfamide in combination with doxorubicin was 2.75 g/m2/day for 5 days. The objective response rate was 83% with a complete response rate of 33% (6/18 patients); the median time to treatment failure was 11.5 months. The median survival has not been reached and will exceed 18 months. We concluded that the recommended dose of ifosfamide in combination with doxorubicin is 2.5 g/m2/day for 5 days. This combination shows promise in stage IV breast cancer.

Post-transplant Lymphoproliferative Disorders: A Rare Case of Primary Pericardial Involvement Epstein-Barr Virus-Correlated in Heart Transplantation.

Post-transplant lymphoproliferative disorders (PTLDs) are considered a fatal consequence of immunosuppression. We report a case of a 52-year-old patient, who underwent a cardiac transplantation and presented undefined recurrent episodes of pleuropericardial effusions without lymphoadenomegaly at chest radiographs and computed tomography. Histopathological analysis of the bioptic pericardium showed a specific chronic inflammation. Monitoring endomyocardial biopsies (EMBs) showed only 1 episodes of greater than grade 2R acute cellular rejection requiring immunosuppressive treatment, mild vasculitis in 2 subsequently EMBs while constantly negative for antibody-mediated rejection or infection. Only a post-mortem examination demonstrated the presence of an aggressive acute non-Epstein-Barr virus (EBV)-related proliferative disorder with unusual primitive localization into the pericardium and with coronary epicardial and intramyocardial necrotizing vasculitis and superimposed occlusive and subocclusive thrombosis. Recurrence of unexplained early pleuropericardial effusion and mild intramyocardial vasculitis should raise the suspicion of PTLD requiring reduction of immunosuppression, even in the setting of negative intramyocardial cellular infiltrate and tissue EBV-negative molecular assessment.

Tension ball valve mucus plug in asthma.

This report describes a patient with status asthmaticus and respiratory failure in whom profound hypoxemia developed during mechanical ventilation. During the hypoxemic episode, breath sounds were absent over the left lung, and chest radiography revealed a hyperlucent left hemithorax with tension shift of the mediastinum to the right. The presence of lung markings in the left lung on radiography eliminated the possibility of tension pneumothorax and led to the diagnosis of tension mediastinal shift secondary to a ball valve obstruction by a central mucus plug. Bronchoscopic lung lavage removed the mucus plug, thereby correcting the hypoxemia. Recognition of this previously undescribed acute complication of mechanical ventilation in status asthmaticus is essential so that confusion with tension pneumothorax is avoided and appropriate therapy instituted.

(2-exo-3-endo)-2-Aryltropane-3-carboxylic esters, a new class of narcotic antagonists.

Tropanes 4 bearing an exo aromatic group on carbon-2, an endo-carbomethoxy group on carbon-3, and either a methyl group or a hydrogen on the nitrogen were found to be narcotic antagonists which were devoid of demonstrable analgesic activity. The activity resided in the 1S enantiomer. Compound 4 (R = m-hydroxyphenyl) showed an AD50 of 0.37 mg/kg sc and 1.8 mg/kg po (rats) as an antagonist in the Harris-Pierson modification of the D'Amour-Smith test. The tropane esters for this study were prepared by a Grignard reaction which gave essentially complete 1,4-addition in the absence of copper salts. Nearly equal quantities of esters epimeric at carbon-3 were formed.