A randomized, double-blind, placebo-controlled safety and acceptability study of two Invisible Condom® formulations in women from Cameroon

Background

The objectives of this clinical trial were to evaluate the safety, tolerance and acceptability of two gel formulations of the Invisible Condom®: (i) the polymer alone and (ii) the polymer-containing sodium lauryl sulfate (SLS) compared to placebo when applied intravaginally with our unique applicator in sexually abstinent and active woman volunteers.

Study Design

A randomized, doubled-blind, placebo-controlled study in healthy women from Yaoundé, Cameroon. Two hundred sixty women were randomized into three gel arms: (a) gel alone, (b) gel plus SLS and (c) placebo gel. Thirty-seven sexually abstinent women applied gel intravaginally once a day for 14 days, while 75, 74 and 74 sexually active women applied gel intravaginally once, twice or three times daily for 14 days, respectively.

Results

Retention rate was high at 85% and 221 women applied the two products and the placebo for a total of 6005 times. Nugent score, H₂O₂-producing lactobacilli and vaginal pH were stable throughout the study and were not affected by the study products. Colposcopy showed neither genital ulceration nor mucosal lesions. No study product-related serious adverse events were reported. The majority of reported adverse events were mild or moderate and largely similar in all 3 arms. Satisfaction questionnaire showed that the gel formulations and applicator were generally comfortable and acceptable.

Conclusion

The Invisible Condom® formulations and applicator were found to be comfortable, well tolerated and acceptable when applied intravaginally once, twice or thrice daily for 14 days. Thus, expanded safety evaluation is warranted.     

Nectin-4 is a new histological and serological tumor associated marker for breast cancer

Introduction

Breast cancer is a complex and heterogeneous disease at the molecular level. Evolution is difficult to predict according to classical histoclinical prognostic factors. Different studies highlight the importance of large-scale molecular expression analyses to improve taxonomy of breast cancer and prognostic classification. Identification of new molecular markers that refine this taxonomy and improve patient management is a priority in the field of breast cancer research. Nectins are cell adhesion molecules involved in the regulation of epithelial physiology. We present here Nectin-4/PVRL4 as a new histological and serological tumor associated marker for breast carcinoma.

Methods

Expression of Nectin-4 protein was measured on a panel of 78 primary cells and cell lines from different origins and 57 breast tumors by FACS analysis and immunohistochemistry (IHC), respectively. mRNA expression was measured by quantitative PCR. Serum Nectin-4 was detected by ELISA and compared with CEA and CA15.3 markers, on panels of 45 sera from healthy donors, 53 sera from patients with non-metastatic breast carcinoma (MBC) at diagnosis, and 182 sera from patients with MBC. Distribution of histological/serological molecular markers and histoclinical parameters were compared using the standard Chi-2 test.

Results

Nectin-4 was not detected in normal breast epithelium. By contrast, Nectin-4 was expressed in 61% of ductal breast carcinoma vs 6% in lobular type. Expression of Nectin-4 strongly correlated with the basal-like markers EGFR, P53, and P-cadherin, and negatively correlated with the luminal-like markers ER, PR and GATA3. All but one ER/PR-negative tumors expressed Nectin-4. The detection of Nectin-4 in serum improves the follow-up of patients with MBC: the association CEA/CA15.3/Nectin-4 allowed to monitor 74% of these patients compared to 67% with the association CEA/CA15.3. Serum Nectin-4 is a marker of disease progression, and levels correlate with the number of metastases (P = 0.038). Serum Nectin-4 is also a marker of therapeutic efficiency and correlates, in 90% of cases, with clinical evolution.

Conclusion

Nectin-4 is a new tumor-associated antigen for breast carcinoma. Nectin-4 is a new bio-marker whose use could help refine breast cancer taxonomy and improve patients' follow-up. Nectin-4 emerges as a potential target for breast cancer immunotherapy.     

Successful mitigation of delayed intestinal radiation injury using pravastatin is not associated with acute injury improvement or tumor protection

PURPOSE: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition. METHODS AND MATERIALS: Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments. RESULTS: Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury. CONCLUSION: Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible.     

Quality index for the quantification of the information recorded along standard microelectrode tracks to the subthalamic nucleus in parkinsonian patients.

OBJECTIVE: To quantify the usefulness of the neuronal activity recorded on a standard microelectrode track to the subthalamic nucleus (STN) for the determination of the transition between the thalamus and the STN. METHODS: The study is based on analysis of 689 extracelullar single units recorded on 70 tracks passing through the thalamus and the STN. Using four neuron parameters that were correlated with electrode depth, a quality index (QI) for each track was computed and compared with the subjective assessment by the electrophysiologist of the track quality. RESULTS: Subjectively, the transition between the thalamus and the STN was detected in 49 tracks (usual track) and not detected on 21 tracks (unusual tracks). Objectively, spike frequency, cell burst index (BI), signal relative root mean square (RMS) and spike relative amplitude were correlated with electrode depth and used to compute track QI. The average QI index of usual and unusual tracks was 0.25 +/- 0.9 and 0.85 +/- 0.15 (mean +/- confidence interval at P < 0.001), respectively. In 20 patients, QI correlates with post-operative measurement of electrode length in the STN. CONCLUSION: These results demonstrate that simple statistical analysis taking into account the variation of single-unit characteristics with electrode depth can discriminate between useful and useless tracks for the determination of the STN localisation.     

The issue of dialysis withdrawal and palliative cares. A 3-year retrospective study carried out at Grenoble university teaching hospital development of a decision-making tool

Dialysis-related constraints encourage questioning about discontinuation of treatment. In France, the 04/22/2005 law, related to patients' rights and end-of-life issues, defines bounds to treatment withdrawal, authorizing it in specific conditions, to avoid foolish obstinacy. Shortly before the publication of this law, a study has been conducted at Grenoble University Teaching Hospital, involving 31 patients followed by the dialysis service and the palliative care service, in order to analyse the circumstances in which withdrawals from dialysis happen. These patients were old and their general condition was very poor. After initiation of the questioning, treatment was removed in older patients and in those who had been dialysed for short time, which suggests they may have poor adaption to the treatment. No dialysis withdrawal was ever decided without the patient consent or without his nearest and dearest consent. After multidisciplinary discussions, a decision-making tool for dialysis withdrawal has been developed, with a view to be a starting point in the thinking process, for each decision to be adapted to each situation. This tool emphasizes the importance of time and collegial consultation in the decision-making process. It points out to that the decision lies with the referent nephrologist. After withdrawing dialysis, palliative cares must be implemented, since stopping the treatment does not mean stopping cares.     

Long‐term effects of neonatal hippocampal lesions on novelty preference in monkeys

In a recent longitudinal study to assess the development of incidental recognition memory processes in monkeys, we showed that the effects of neonatal hippocampal lesions did alter incidental recognition memory only when the animals reached the juvenile period (Zeamer et al., 2010 ). The current follow‐up study tested whether this incidental memory loss was long‐lasting, i.e., present in adulthood, or only transitory, due to functional compensation with further brain maturation. The same animals with neonatal hippocampal lesions and their sham‐operated controls were re‐tested in the visual paired‐comparison task when they reached adulthood (48 months). The results demonstrated that, at least for easily discriminable color pictures of objects, the involvement of the hippocampus was only transitory, given that when re‐tested as adults, animals with neonatal hippocampal lesions performed as well as sham‐operated controls at all delays. Yet, significant recognition memory impairment was re‐instated when the discriminability of the stimuli was made more difficult (black/white pictures of similar objects). The data demonstrate profound functional remodeling within the hippocampus and its interactions with different medial temporal lobe structures from the juvenile period to adulthood, which is substantiated by a parallel morphological maturation of hippocampal intrinsic circuits (Lavenex et al., 2007a ; Jabès et al., 2011 ). © 2013 Wiley Periodicals, Inc.     

Psychological adjustment of critically injured patients three months after an unexpected,potentially life‐threatening accident

? Cognitive processing and meaning theories suggest that a patient’s psychological adjustment following a traumatizing event depends on an ability to cognitively integrate the trauma event and restore a sense of meaning in life. These processes may be facilitated by using coping strategies such as sharing concerns, mobilizing support, and reframing. ? A correlational study explored the magnitude of the relationships between psychological adjustment, cognitive processing, sense of meaning, and coping strategies in critically injured patients 3 months after a potentially life‐threatening injury. ? Fifty‐one critically injured patients completed the Brief Symptom Inventory, Bradburn’s Psychological Well‐Being Scale, Impact of Events Scale, the Meaning‐of‐Illness Questionnaire, and Family Crisis‐Oriented Personal Evaluation Scale in face‐to‐face interviews 8–12 weeks after the accident. Bivariate and partial correlation coefficients were used to test the main hypothesis, and Pearson correlation coefficients, to address the three research questions. ? The main hypothesis that psychological adjustment will be significantly related to cognitive processing, sense of meaning, and use of coping strategies in critically injured patients 3 months after the accident was partially upheld. ? Depressive symptomatology was found to be significantly associated with increased cognitive processing efforts and a decreased ability to acknowledge the accident’s negative effects on the self. ? In contrast, psychological well‐being was found to be significantly associated with decreased cognitive processing efforts and an increased ability to acknowledge the accident’s negative effects on the self. ? Restoring a sense of meaning, however, was found to be unrelated to sharing concerns, mobilizing support and re‐framing. The potential theoretical and clinical implications of the findings for nursing practice are discussed.