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Sabrina Bimonte,1,* Piergiacomo Di Gennaro,2,* Anna Crispo,2 Sergio Coluccia,2 Assunta Luongo,2 Alfonso Amore,3,4 Egidio Celentano,2 Francesco Del Prato,1 Daniela Schiavo,1 Davide Nocerino,1 Marco Cascella,5 Arturo Cuomo1 1Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 2Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 3Melanoma and Sarcoma Surgery Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 4PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy; 5Department of Medicine, University of Salerno, Salerno, Italy*These authors contributed equally to this workCorrespondence: Anna Crispo, Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Via Mariano Semmola 53, Naples, Italy, Tel +39 081 17770298, Email a.crispo@istitutotumori.na.itPurpose: Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that “breaks through” a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) subtype occurs in the absence of any specific activity. Evidence showed that gender differences exist in pain response sensitivity and clinical pain risk. This analysis aimed to signify the gender differences for the NP-BTcP phenomenon.Patients and Methods: This is a secondary analysis of the Italian Oncologic Pain multiSetting-Multicentric Survey (IOPS-MS), the largest study on BTcP. The subset of NP-BTcP cases for non-gender-specific cancer was considered. Univariable and multivariate analyses were conducted to identify gender differences for the NP-BTcP profile about its intensity, number of episodes per day, and type. A metastatic status-stratified analysis was performed to compare gender with the main clinical variables among the population with NP-BTcP.Results: Males exhibited a higher occurrence of BTcP in the thorax region compared to females (15% vs 11%, respectively, p = 0.03). Males also had a higher onset of BTcP, a higher BTcP therapy dosage (33% vs 28%, p = 0.04, mean: 201 vs 186, p = 0.02) and a lower Karnofsky score (mean: 46.9 vs 49.2, p = 0.03) compared to females. Similar gender differences were found for metastatic patients in the BTcP site (14% vs 8.5%, respectively; p = 0.01), peak onset (33% vs 27%, p = 0.02), BTcP therapy dosage (199 vs 185, p=0.04), and Karnofsky score (mean 47.5 vs 50.4, p = 0.009). Phenotype 2 was more characterized by non-metastatic males (41% vs 23%, p = 0.020) while non-metastatic females presence was predominant among others.Conclusion: In this study, gender differences according to site, onset and dosage of BTcP were found. The phenotype characterization of BTcP needs to be further investigated for a possible useful function in the management of cancer-related pain in non-metastatic patients.Keywords: non-predictable breakthrough cancer pain, gender cancer pain, cluster analysis

The magnetic properties of pressed pellets of ClO4- partially doped poly(3-hexylthiophene) have been investigated in the range from 5 to 300 K and a ferromagnetic phase was observed at room temperature. This behavior was associated to polaron interaction because the saturation magnetization, remanent magnetization, and coercive field, change with the reversible potential that modulates the doping level of the samples. This effect is a consequence of the Nernst potential describes the ratio among reduced sites, polarons and bipolarons in the sample. The results also show that the ferromagnetic phase vanishes when the samples undergo a thermal annealing or are stored under atmospheric conditions for a long period of time. The absence of contaminants such as Co, Fe and Ni was determined using inductively coupled plasma tandem mass spectrometry with ppb resolution. These results support that the ferromagnetic behavior observed in samples is intrinsic. [ABSTRACT FROM AUTHOR]

Tapetal Changes in Beagle Dogs following Oral Administration of CGS 14796C, A Potential Aromatase Inhibitor. SCHIAVO, D. M., GREEN, J. D., TRAINA, V. M., SPAET, R., AND ZAIDI, I. (1988) . 10, 329-334. CGS 14796C, m-l-[(4-[(l-imidazolyl)methyl]-cyclohexyl)methyl)imidazole succinate, has been evaluated as a potential aromatase inhibitor. As part of the safety evaluation program, a 3-month oral toxicity study was performed in which beagle dogs were administered CGS 14796C by gavage at 5, 15, or 50 mg/kg/day. Ophthalmos-copically, changes in the tapetum lucidum affecting dogs from the 15 and 50 mg/kg dose levels were diffuse areas of pigmentation varying in appearance from a brownish peppered or mottled to a more uniform brown similar to that of the nontapetal area of the fundus. Tapetal reflectivity was absent or markedly reduced. Within the pigmented area, multiple islets (yellow, green, or orange) of tapetal cells were visible, suggestive of destruction of the tapetum. In no instance was retinal destruction, edema, vascular changes, or detachment observed. Ophthalmoscopic examinations performed during recovery revealed changes of slight increase in tapetal islets, suggestive of a slight progression and organization within the tapetum followed by an arrest of the toxic insult within the tapetal tissue. At light and electron microscopic examination of the ocular tissues, the lesions were tapetal cell degeneration/atrophy. These results demonstrated that the taptetum lucidum was a target tissue of toxicity for CGS 14796C, and indicated that the findings are without toxicological significance in atapetal species, including man, whose globes do not have this Structure. [ABSTRACT FROM PUBLISHER]

Methylene blue (AM) was immobilised on surface of the silica gel modified with niobium oxide. This material was incorporated in a carbon paste electrode, which showed a redox couple in a potential of E= -113 mV vs SCE in KCl solution at pH 7.0. The formal potential, in 0.5 mol L-1 KCl at pH 7.0, shifted about 290 mV towards more positive values compared to those observed for AM solubilized in aqueous solution. The dependence on the formal potential with solution pH between 2 and 7 was much lower than those observed for AM solubilized in aqueous solution.

Pain is a debilitating phenomenon that dramatically impairs the quality of life of patients. Many chronic conditions, including cancer, are associated with chronic pain. Despite pharmacological efforts that have been conducted, many patients suffering from cancer pain remain without treatment. To date, opioids are considered the preferred therapeutic choice for cancer-related pain management. Unfortunately, opioid treatment causes side effects and inefficiently relieves patients from pain, therefore alternative therapies have been considered, including Cannabis Sativa and cannabinoids. Accumulating evidence has highlighted that an increasing number of patients are choosing to use cannabis and cannabinoids for the management of their soothing and non-palliative cancer pain and other cancer-related symptoms. However, their clinical application must be supported by convincing and reproducible clinical trials. In this review, we provide an update on cannabinoid use for cancer pain management. Moreover, we tried to turn a light on the potential use of cannabis as a possible therapeutic option for cancer-related pain relief., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In oncological disease, a definition of pain as total suffering emerges. This complex phenomenon is characterized by the simultaneous involvement of several dimensions (bodily, cognitive, emotional, family, social, and cultural) held together by a bond of mutual interdependence. Cancer pain is pervasive and affects all aspects of a person's life. It alters the individual's perspective and perception of the world, creating a sense of stagnation and uncertainty characterized by anguish and precariousness. It threatens the sense of personal identity and extends its influence on the entire relational system in which the patient is inserted. The pain of the individual affects the entire family system: priorities, needs, rhythms, methods of communication, and family relationships change to cope with the devastating pathological condition. The relationship between pain and emotions is close as cancer pain stimulates powerful emotional experiences that exert a significant influence on the modalities the patient adopts to manage pain. In addition to the emotional aspects, cognitive factors contribute to characterizing the pain experience: each individual has a set of beliefs, convictions, expectations, and ways of understanding pain built on his/her life experiences and socio-cultural context. Careful understanding of these aspects is of fundamental importance in clinical practice as they modulate the whole pain experience. Furthermore, the patient's experiences with pain can affect the overall response to the disease and have a negative impact on functionality and well-being. Consequently, the impact of cancer pain extends to the patient's family and social network. Because of the multicomponent nature of the cancer pain phenomenon, there is a need for an integrated and multidimensional approach to its study and treatment. This approach must provide for the activation of a flexible setting oriented to the patient's global care and encompassing the totality of the biopsychosocial needs. In addition to the symptom assessment, recognizing the "person" is the challenge that must be taken in the authentic space of a relationship that nourishes and sustains itself. The aim is to go through the experience of pain together with the patient in the direction of consolation and hope.

Although proper pain evaluation is mandatory for establishing the appropriate therapy, self-reported pain level assessment has several limitations. Data-driven artificial intelligence (AI) methods can be employed for research on automatic pain assessment (APA). The goal is the development of objective, standardized, and generalizable instruments useful for pain assessment in different clinical contexts. The purpose of this article is to discuss the state of the art of research and perspectives on APA applications in both research and clinical scenarios. Principles of AI functioning will be addressed. For narrative purposes, AI-based methods are grouped into behavioral-based approaches and neurophysiology-based pain detection methods. Since pain is generally accompanied by spontaneous facial behaviors, several approaches for APA are based on image classification and feature extraction. Language features through natural language strategies, body postures, and respiratory-derived elements are other investigated behavioral-based approaches. Neurophysiology-based pain detection is obtained through electroencephalography, electromyography, electrodermal activity, and other biosignals. Recent approaches involve multimode strategies by combining behaviors with neurophysiological findings. Concerning methods, early studies were conducted by machine learning algorithms such as support vector machine, decision tree, and random forest classifiers. More recently, artificial neural networks such as convolutional and recurrent neural network algorithms are implemented, even in combination. Collaboration programs involving clinicians and computer scientists must be aimed at structuring and processing robust datasets that can be used in various settings, from acute to different chronic pain conditions. Finally, it is crucial to apply the concepts of explainability and ethics when examining AI applications for pain research and management., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Marco Cascella et al.)

Background/aim: Telemedicine, the remote delivery of healthcare services, represents a great opportunity for cancer pain management. A care model of telemedicine that combines remote visits and hospital access could be an effective and safe strategy for pain management of cancer patients., Patients and Methods: A retrospective study was conducted using the dataset of the telemedicine program at the Istituto Nazionale Tumori of Naples, Italy for assessing the efficacy of a telehealth-based model of care. Demographic, clinical, and process variables were investigated., Results: A total of 226 cases and 489 visits were included in the analysis. The mean age of patients was 63.4 years (SD=12.4 years), and no sex differences were observed. Approximately 55% of patients were ECOG-PS ≤2 and 87% suffered from metastatic disease. More than half of the patients were treated with high doses of opioids. Each patient had a mean of 2 remote visits and half of the patients had more than 1 telehealth consultation. The dropout ratio was 5.3%. Most visits (n=472) were conducted on patients in the Campania Region, Italy. The maximum covered distance from the Cancer Center and the patients' location was 555.22 Km. A significant difference in the overall number of visits (p=0.006) and the number of pro-capita remote visits (p=0.010) was found, in favor of the group of patients treated before the end of the Covid-19 emergency in Italy, compared to those treated after the pandemic., Conclusion: Despite various positive outcomes, the analysis highlights several weaknesses, such as the need to assist patients with advanced and non-advanced disease located outside the regional territory. Overall, the telehealth processes should be adapted to post-pandemic scenarios towards their implementation in routine clinical practice., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The most effective strategy for managing cancer pain remotely should be better defined. There is a need to identify those patients who require increased attention and calibrated follow-up programs. Methods: Machine learning (ML) models were developed using the data prospectively obtained from a single-center program of telemedicine-based cancer pain management. These models included random forest (RF), gradient boosting machine (GBM), artificial neural network (ANN), and the LASSO−RIDGE algorithm. Thirteen demographic, social, clinical, and therapeutic variables were adopted to define the conditions that can affect the number of teleconsultations. After ML validation, the risk analysis for more than one remote consultation was assessed in target individuals. Results: The data from 158 patients were collected. In the training set, the accuracy was about 95% and 98% for ANN and RF, respectively. Nevertheless, the best accuracy on the test set was obtained with RF (70%). The ML-based simulations showed that young age (<55 years), lung cancer, and occurrence of breakthrough cancer pain help to predict the number of remote consultations. Elderly patients (>75 years) with bone metastases may require more telemedicine-based clinical evaluations. Conclusion: ML-based analyses may enable clinicians to identify the best model for predicting the need for more remote consultations. It could be useful for calibrating care interventions and resource allocation.

Background: The coronavirus disease 2019 (COVID-19) pandemic would have particularly affected acute stroke care. However, its impact is clearly inherent to the local stroke network conditions. We aimed to assess the impact of COVID-19 pandemic on acute stroke care in the Lyon comprehensive stroke center during this period., Methods: We conducted a prospective data collection of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) during the COVID-19 period (from 29/02/2020 to 10/05/2020) and a control period (from 29/02/2019 to 10/05/2019). The volume of reperfusion therapies and pre and intra-hospital delays were compared during both periods., Results: A total of 208 patients were included. The volume of IVT significantly decreased during the COVID-period [55 (54.5%) vs 74 (69.2%); p = 0.03]. The volume of MT remains stable over the two periods [72 (71.3%) vs 65 (60.8%); p = 0.14], but the door-to-groin puncture time increased in patients transferred for MT (237 [187-339] vs 210 [163-260]; p < 0.01). The daily number of Emergency Medical Dispatch calls considerably increased (1502 [1133-2238] vs 1023 [960-1410]; p < 0.01)., Conclusions: Our study showed a decrease in the volume of IVT, whereas the volume of MT remained stable although intra-hospital delays increased for transferred patients during the COVID-19 pandemic. These results contrast in part with the national surveys and suggest that the impact of the pandemic may depend on local stroke care networks.

Lung cell injury and repair is a hallmark of the acute respiratory distress syndrome (ARDS). Lung protective mechanical ventilation strategies in these patients may lead to hypercapnia (HC). Although HC has been explored in the clinical context of ARDS, its effect upon alveolar epithelial cell (AEC) wounding and repair remains poorly understood. We have previously reported that HC alters the likelihood of AEC repair by a pH-sensitive but otherwise unknown mechanism. Adenylate cyclase (AC) is an attractive candidate as a putative AEC CO 2 sensor and effector as it is bicarbonate sensitive and controls key mediators of AEC repair. The effect of HC on AC activity and plasma membrane (PM) wound repair was measured in AEC type 1 exposed to normocapnia (NC, 40 Torr) or HC (80 Torr), ± tromethamine (THAM) or sodium bicarbonate (HCO3) ± AC probes in a micropuncture model of AEC injury relevant to ARDS. Intracellular pH and AC activity were measured and correlated with repair. HC decreased intracellular pH 0.56, cAMP by 37%, and absolute PM repair rate by 26%. Buffering or pharmacologic manipulation of AC reduced or reversed the effects of HC on AC activity (THAM 103%, HCO 3 113% of NC cAMP, ns; Forskolin 168%, p < 0.05) and PM repair (THAM 87%, HCO 3 108% of NC likelihood to repair, ns; Forskolin 160%, p < 0.01). These findings suggest AC to be a putative AEC CO 2 sensor and modulator of AEC repair, and may have implications for future pharmacologic targeting of downstream messengers of the AC-cAMP axis in experimental models of ARDS.

Background and Objective: The main purpose of treatment in patients with malignant pleural effusion (MPE) is symptom palliation. Currently, patients undergo repeat thoracenteses prior to receiving a definitive procedure as clinicians are not aware of the risk factors associated with fluid recurrence. The primary objective of this study was to identify risk factors associated with recurrent symptomatic MPE., Methods: Retrospective multicentre cohort study of patients who underwent first thoracentesis was performed. The primary outcome was time to fluid recurrence requiring intervention in patients with evidence of metastatic disease. We used a cause-specific hazard model to identify risk factors associated with fluid recurrence. We also developed a predictive model, utilizing Fine-Gray subdistribution hazard model, and externally validated the model., Results: A total of 988 patients with diagnosed metastatic disease were included. Cumulative incidence of recurrence was high with 30% of patients recurring by day 15. On multivariate analysis, size of the effusion on chest X-ray (up to the top of the cardiac silhouette (hazard ratio (HR): 1.84, 95% CI: 1.21-2.80, P = 0.004) and above the cardiac silhouette (HR: 2.22, 95% CI: 1.43-3.46, P = 0.0004)), larger amount of pleural fluid drained (HR: 1.06, 95% CI: 1.04-1.07, P < 0.0001) and higher pleural fluid LDH (HR: 1.008, 95% CI: 1.004-1.011, P < 0.0001) were associated with increased hazard of recurrence. Negative cytology (HR: 0.52, 95% CI: 0.43-0.64, P < 0.0001) was associated with decreased hazard of recurrence. The model had low prediction accuracy., Conclusion: Pleural effusion size, amount of pleural fluid drained, LDH and pleural fluid cytology were found to be risk factors for recurrence., (© 2018 Asian Pacific Society of Respirology.)

This work describes a procedure using the recently proposed standard dilution analysis (SDA) calibration method for the determination of As, Cr and Ni in concentrated HNO 3 and HCl by inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). Because of the low contaminant levels, and consequently low limits of detection required for these reagents (commonly used in trace element analysis and the semiconductor industry), samples were minimally diluted. The analysis of concentrated acids can result in matrix/transport effects, which may compromise accuracy in ICP-MS determinations. High-chlorine content samples are also challenging for As and Cr determination due to the formation of polyatomic species such as 40 Ar 35 Cl + and 35 Cl 16 OH + , which overlap the only As isotope, 75 As + , and the main Cr isotope, 52 Cr + , respectively. The combination of SDA and ICP-MS/MS was evaluated to overcome matrix, transport and spectral interferences in order to increase accuracy, precision and sample throughput. The performance of SDA was compared with the traditional methods of external standard calibration (EC), internal standardization (IS), and standard additions (SA). The limits of detection for SDA were calculated as 6, 10, and 30ngL -1 for As, Cr, and Ni, respectively. Recoveries for spike experiments using the new method were in the 90-114% range for all analytes. The procedure described here provides similar or even better analytical performance in comparison with EC, IS and SA., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A 51-year-old man presented with progressively worsening lung infiltrates and respiratory failure. Extensive investigations including bronchoscopy with bronchoalveolar lavage and conventional transbronchial forceps biopsies failed to establish the diagnosis. After transfer to our institution, he underwent repeat bronchoscopy with transbronchial cryobiopsy, which provided large, high-quality biopsy specimens establishing the diagnosis of parenchymal diffuse large B-cell lymphoma.

A method for the determination of sulfur in biodiesel samples by inductively coupled plasma optical emission spectrometry which uses microemulsion for sample preparation and the summation of the intensities of multiple emission lines has been developed. Microemulsions were prepared using 0.5 mL of 20% v/v HNO(3), 0.5 mL of Triton X-100, 2-3 mL of biodiesel sample, and diluted with n-propanol to a final volume of 10 mL. Summation of the emission intensities of multiple sulfur lines allowed for increased accuracy and sensitivity. The amounts of sulfur determined experimentally were between 2 and 7 mg L(-1), well below legislative standards for many countries. Recoveries obtained ranged from 72 to 119%, and recoveries obtained for the 182.562 nm line were slightly lower. This is most likely due to its lower sensitivity. Using microemulsion for sample preparation and the summation of the intensities of multiple emission lines for the successful determination of sulfur in biodiesel has been demonstrated., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The applicability of thermospray flame furnace atomic absorption spectrometry (TS-FF-AAS) was evaluated for direct determination of Cu, Cd and Pb in wines and grape juices. The developed procedure does not require preliminary acid digestion of the samples. The optimum conditions for determination of Cu, Cd and Pb in wines were studied and the performance was compared to those typically obtained by flame atomic absorption spectrometry (FAAS). A sample volume of 150 microL was introduced into a heated nickel tube at a flow rate of 0.54 mLmin(-1) and 0.14 molL(-1) HNO(3) was used as sample carrier flowing at 2.5 mLmin(-1) for determining all analytes. The effect of ethanol concentrations on Cu, Cd and Pb absorbance signals were studied. All determinations were carried out by adopting optimized conditions and quantification was based on the standard additions method. Limits of detection (LOD) of 12.9, 1.8 and 5.3 microgL(-1) (n=14) for Cu, Cd and Pb, respectively, were obtained for wine samples (3sigma(blank)/slope, n=14). Relative standard deviations (R.S.D., %) of 2.7, 2.1 and 2.6 for Cu, Cd and Pb, were obtained (n=6) for wine samples. The values determined for grape juice samples were similar to these ones. The analytical throughput was 45 determinations h(-1) and accuracy was checked by addition-recovery experiments.

Objective: This study evaluated whether a supplementary skills training program improved work outcomes for clients enrolled in supported employment programs., Methods: Thirty-five recently employed clients with severe mental illness who were receiving supported employment services at a free-standing agency were randomly assigned to participate in either the workplace fundamentals program, a skills training program designed to make work more "successful and satisfying," or treatment as usual. Knowledge of workplace fundamentals (for example, identifying workplace stressors, problem solving, and improving job performance) was assessed at baseline and at nine months; employment outcomes and use of additional vocational services were tracked for 18 months., Results: Clients in the workplace fundamentals group (N=17) improved more in knowledge of workplace fundamentals than those in the control group (N=18) at the nine-month follow-up, but the two groups did not differ in the number of hours or days worked, salary earned, or receipt of additional vocational services over the 18-month period. In general, clients in this study had higher educational levels and better employment outcomes than clients in most previous studies of supported employment, making it difficult to detect possible effects of the skills training intervention on work., Conclusions: Supplementary skills training did not improve work outcomes for clients who were receiving supported employment.

The study presents mortality rates for lung cancer in the town of Casale Monferrato, where the largest Italian asbestos cement-plant was located. Cases of lung cancer dying in 1989-94 were exhaustively searched for in the register of deaths. Each case of lung cancer has been identified as ever or never employed in the factory with a linkage to the rosters of employees in the plant. Women were also identified as ever or never married to an asbestos-cement worker. The number of person-years at risk for asbestos cement workers and their wives was measured on the basis of the most recent follow-up. Mortality rates were computed separately for those exposed (workers and wives of workers) and for those with no evidence of exposure. Mortality rates for non-exposed were similar to rates in Piedmont (the region where Casale is located). The relative risk (ever exposed vs. never exposed) was 2.8 among men and 2.1 among women. Attributable risk among the exposed was 64.5% for men and 53.1% for women while among the general population it was 18.1% for men and 13.2% for women. The study confirms the dramatic effect of occupational asbestos exposure in Casale Monferrato but does not suggest an increase in lung cancer mortality among people with no occupational activity in the asbestos-cement production.

In a recent text by Grant (3), approximately 2,800 substances are listed as having some type of untoward effect on ocular tissue. The kinds of substances that may cause toxic damage/effects range from carbolic acid (2) to oxygen (1). It is the purpose of this communication to briefly review ocular toxicology as investigated in laboratory animals.

Multifocal retinal dysplasia was diagnosed clinically in twenty-four of twelve hundred (2.0% incidence) LAK:LVG (SYR) Syrian Hamsters. The affected hamsters were part of twelve hundred animals to be used in oncogenic studies. Ther dysplastic retina were detected during ophthalmoscopic examinations of hamsters as young as 6 weeks and as old as 9 months. Ophthalmoscopically, the dysplastic foci varied from retinal streaks, sometimes called vermiform, to small, generally circular areas of cream-colored depigmentations. Blindness or othe apparent visual defects were not seen nor were the dysplasias associated with a generalized syndrome of disease. Histologic examination of the affected hamsters revealed focal dysplasias limited to the retina and were manifested as invaginations and rosette-like structures composed of elements of the photoreceptor layer, outer limiting membrane and outer nuclear layer. This paper describes the first incidence of a congenital retinal dysplasia found in an outbred strain of Syrian Hamster LAK:LVG (SYR), and correlates the ophthalmoscopic appearance and histopathology. In addition, a procedure for maintaining prolonged mydriasis for funduscopic photography is presented.

SCH 19927 [R,R)-(-)-2-Hydroxy-5-[1-hydroxy-2-[(1-methyl -3-phenylpropyl)amino]ethyl]benzamide hydrochloride) is a beta-adrenergic blocking agent which has vasodilating properties. In a subchronic oral toxicity study in beagle dogs, SCH 19927 was given by gavage at doses of 30, 60, and 90 mg/kg. Lesions were observed at weeks 13 and 19 in the tapetum lucidum, a light reflecting structure of the eye. The lesions consisted of focal to multifocal areas of discoloration of the tapetal portion of the ocular fundus, pigmentation in the tapetal area, and, in one dog, subretinal edema resulting in a focal retinal detachment. Light and electron microscopic examination of the ocular lesions demonstrated tapetal cell degeneration and necrosis with macrophages, lymphocytes, and occasional plasma cells in the tapetum and adjacent choroid. Local cellular infiltrates within the retina internal to the pigmented epithelium were observed in one dog (60 mg/kg) which was demonstrated to have focal retinal edema during the study. In a repeat study the lesion again occurred in tapetal beagle dogs but not in atapetal beagle dogs (90 mg/kg) or cynomolgous monkeys (360 mg/kg). The lesion had not occurred in a previous subchronic study in albino rats. These results demonstrated that the tapetum lucidum was a target organ of toxicity for SCH 19927 and indicated that the finding was without observable toxicological significance in animals, including man, whose eyes do not have this structure.

A new and rapid method for testing low levels of ocular irritation using a balanced incomplete block design, a new grading system, and statistical analysis of the results, has been developed. Two drops (0.1 ml) of 1 of 5 ophthalmic solutions were instilled into the conjunctival sac of the right or left eye of each of 10 New Zealand white [Deb:(NZW)] rabbits hourly for 9 hr on 4 consecutive da. Before the study and before the first instillation on each day, the eyes were examined with a direct ophthalmoscope, and the reactions were graded according to a modification of the system in the illustrated Guide for Grading Eye Irritation by Hazardous Substances. The new procedure showed that 1 of the 5 solutions elicited a significantly more severe (p less than or equal to 0.05) ocular response of redness, chemosis, and discharge than did any of the other 4 solutions. Previous testing of this solution in rabbits by standard laboratory procedures and the Draize method of grading ocular irritation failed to detect these reactions.