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Context: The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk.Objective: To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer.Design, Setting, and Participants: Prospective study of 257 patients with pN0 colorectal cancer enrolled between March 2002 and June 2007 at 9 US and Canadian centers (7 academic medical centers and 2 community hospitals) provided 2570 fresh lymph nodes measuring 5 mm or larger for histopathology and GUCY2C messenger RNA analysis. Patients were followed up for a median of 24 months (range, 2-63 months) for disease recurrence or death.Main Outcome Measures: Time to recurrence (primary outcome) and disease-free survival (secondary outcome) relative to expression of GUCY2C in lymph nodes.Results: Thirty-two patients (12.5%) had lymph nodes negative for GUCY2C (pN0 [mol-]), and all but 2 remained free of disease during follow-up (recurrence rate, 6.3%; 95% confidence interval [CI], 0.8%-20.8%). Conversely, 225 patients (87.5%) had lymph nodes positive for GUCY2C (pN0 [mol+]), and 47 developed recurrent disease (20.9%; 95% CI, 15.8%-26.8%) (P = .006). Multivariate analyses revealed that GUCY2C in lymph nodes was an independent marker of prognosis. Patients who were pN0 (mol+) exhibited earlier time to recurrence (adjusted hazard ratio, 4.66; 95% CI, 1.11-19.57; P = .04) and reduced disease-free survival (adjusted hazard ratio, 3.27; 95% CI, 1.15-9.29; P = .03).Conclusion: Expression of GUCY2C in histologically negative lymph nodes appears to be independently associated with time to recurrence and disease-free survival in patients with pN0 colorectal cancer. [ABSTRACT FROM AUTHOR]

Objective: A Knowledge, Attitudes and Practices (KAP) study was conducted in three villages of Bekily District in southern Madagascar prior to the implementation of a health education programme with children. The participatory learning concept of the Child-to-Child approach was followed to involve the children in the planning and implementation of the programme, which was covered by the German Agency for Technical Cooperation.Design: To this effect, qualitative research methods such as Participatory Learning and Action techniques (focus group discussions, mapping and matrix ranking, etc.) were applied.Subjects: The survey was conducted between August and December 1999. It involved a total of 55 school-aged children (6-14 years) along with 21 mothers and 34 fathers, representing different ethnic groups and educational backgrounds.Results: The results show that children's KAP related to health and nutrition strongly reflect those of adults. They are not aware of a possible link between bad hygiene and the occurrence of diseases. According to them, diarrhoea or malaria is caused by consuming too large amounts of certain foods. Even if they know about certain elementary hygiene behaviours, they do not practise this in their everyday life.Conclusion: A major objective of the health education programme for children should be to tackle the discrepancy between hygiene-related knowledge and behaviour. Through the participatory study approach the children revealed their ability to contribute to the programme development. In using appropriate communication channels, the Child-to-Child health education programme is expected to influence the health behaviours of both adults and children. The health education programme should be combined with a literacy programme to address the children's desire to learn reading and writing. [ABSTRACT FROM AUTHOR]

Béla Z Schmidt,1 Jérémy B Haaf,2 Teresinha Leal,2 Sabrina Noel,2 1Stem Cell Biology and Embryology, Department of Development and Regeneration, Katholieke Universiteit Leuven, Leuven, 2Louvain Center for Toxicology and Applied Pharmacology, Université Catholique de Louvain, Brussels, Belgium Abstract: Mutations of the CFTR gene cause cystic fibrosis (CF), the most common recessive monogenic disease worldwide. These mutations alter the synthesis, processing, function, or half-life of CFTR, the main chloride channel expressed in the apical membrane of epithelial cells in the airway, intestine, pancreas, and reproductive tract. Lung disease is the most critical manifestation of CF. It is characterized by airway obstruction, infection, and inflammation that lead to fatal tissue destruction. In spite of great advances in early and multidisciplinary medical care, and in our understanding of the pathophysiology, CF is still considerably reducing the life expectancy of patients. This review highlights the current development in pharmacological modulators of CFTR, which aim at rescuing the expression and/or function of mutated CFTR. While only Kalydeco® and Orkambi® are currently available to patients, many other families of CFTR modulators are undergoing preclinical and clinical investigations. Drug repositioning and personalized medicine are particularly detailed in this review as they represent the most promising strategies for restoring CFTR function in CF. Keywords: high-throughput screening, drug repositioning, personalized medicine, precision medicine, potentiators, correctors

In this paper, we investigate, by means of a computational model, how individuals map quantifiers onto numbers and how they order quantifiers on a mental line. We selected five English quantifiers (few, fewer than half, many, more than half, and most) which differ in truth conditions and vagueness. We collected binary truth value judgment data in an online quantifier verification experiment. Using a Bayesian three-parameter logistic regression model, we separated three sources of individual differences: truth condition, vagueness, and response error. Clustering on one of the model's parameter that corresponds to truth conditions revealed four subgroups of participants with different quantifier-to-number mappings and different ranges of the mental line of quantifiers. Our findings suggest multiple sources of individual differences in semantic representations of quantifiers and support a conceptual distinction between different types of imprecision in quantifier meanings. We discuss the consequence of our findings for the main theoretical approaches to quantifiers: the bivalent truth-conditional approach and the fuzzy logic approach. We argue that the former approach neither can explain inter-individual differences nor intra-individual differences in truth conditions of vague quantifiers. The latter approach requires further specification to fully account for individual differences demonstrated in this study., (© 2024. The Author(s).)

How we perceptually organize a visual stimulus depends not only on the stimulus itself, but also on the temporal and spatial context in which the stimulus is presented and on the individual processing the stimulus and context. Earlier research found both attractive and repulsive context effects in perception: tendencies to organize visual input similarly to preceding context stimuli (i.e., hysteresis, attraction) co-exist with tendencies that repel the current percept from the organization that is most dominant in these contextual stimuli (i.e., adaptation, repulsion). These processes have been studied mostly on a group level (e.g., Schwiedrzik et al., 2014). Using a Bayesian hierarchical model comparison approach, the present study ( N = 75) investigated whether consistent individual differences exist in these attractive and repulsive temporal context effects, with multistable dot lattices as stimuli. In addition, the temporal stability of these individual differences in context effects was investigated, and it was studied how the strength of these effects related to the strength of individual biases for absolute orientations. The results demonstrate that large individual differences in the size of attractive and repulsive context effects exist. Furthermore, these individual differences are highly consistent across timepoints (one to two weeks apart). Although almost everyone showed both effects in the expected direction, not every single individual did. In sum, the study reveals differences in how individuals combine previous input and experience with current input in their perception, and more generally, this teaches us that different individuals can perceive identical stimuli differently, even within a similar context., Competing Interests: Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Protein therapeutics frequently face major challenges, including complicated production, instability, poor solubility, and aggregation. De novo protein design can readily address these challenges. Here, we demonstrate the utility of a topological refactoring strategy to design novel granulopoietic proteins starting from the granulocyte-colony stimulating factor (G-CSF) structure. We change a protein fold by rearranging the sequence and optimising it towards the new fold. Testing four designs, we obtain two that possess nanomolar activity, the most active of which is highly thermostable and protease-resistant, and matches its designed structure to atomic accuracy. While the designs possess starkly different sequence and structure from the native G-CSF, they show specific activity in differentiating primary human haematopoietic stem cells into mature neutrophils. The designs also show significant and specific activity in vivo. Our topological refactoring approach is largely independent of sequence or structural context, and is therefore applicable to a wide range of protein targets., (© 2022. The Author(s).)

Purpose: Meeting the information needs of patients adequately is of high importance in informed consent consultations in surgery. However, information needs often remain unmet in the informed consent consultation. The aim of this study was to assess anxiety and pain in relation to the patients' information needs fulfillment perioperatively., Methods: We applied a question prompt list (QPL) for patients undergoing spine surgery (SN-QPL) before (t1) and a question answering list (SN-QAL) after (t2) the informed consent consultation. The patients additionally completed the "State-Trait Anxiety Operation Inventory" (STOA, cognitive and affective scale) at t1, as well as a pain numerical rating scale (NRS) at t2 and postoperative (t3). We analyzed (1) the association between anxiety, information needs and pain and (2) anxiety and pain scores regarding information needs fulfillment after the consent consultation., Results: A total of n = 118 patients was included. Affective and cognitive state anxiety was only reduced postoperatively (affective p < .001, cognitive p < .05). The higher trait anxiety was, the more patients longed for information at t1-t3 (t1: r = .58/r = .74, each p < .001), (t2: r = .38/r = .49, each p < .001) and (t3: r = .29, p < .01/r = 34, p < .001). Higher grades of trait anxiety resulted in lower information needs fulfilment. Higher state anxiety levels were associated with higher pain levels. Information needs more often remained unfulfilled in high trait and state anxiety patients., Conclusion: Patients' anxiety was associated with (un)fulfilled information needs. Meeting information needs should be optimized in the process of surgeon-patient communication. Adapting the information to the patients' anxiety levels seem to be an effective way to reduce anxiety., (© 2021. The Author(s).)

Background Context: Informed consent is mandatory before surgery and fundamental in the physician-patient interaction. However, communication is sometimes suboptimal., Purpose: The objective was to develop a question prompt list (QPL) for patients undergoing spine surgery (spinal neurosurgery-QPL, "SN-QPL") to encourage them to acquire information during the informed consent consultation (ICC) and assess patients' information needs., Study Design/setting: We conducted a prospective uncontrolled single center study in order to develop a QPL for patients undergoing spine surgery., Patient Sample: Patients inclusion criteria were as follows: (1) planned spinal surgery, (2) age 18 to 80 years, (3) legal capacity, (4) ability to understand and respond to questionnaires, and (5) informed consent., Outcome Measures: We applied the following self-report measures: the developed preliminary QPL with regard to surgery topics and assessment of patients' information needs., Methods: First, we performed a literature review, patient interviews, and two expert rounds. Subsequently, we validated a preliminary SN-QPL including 37 items before and after ICC with regard to importance of items and fulfillment of information needs in 118 patients. A principal component analysis followed by varimax rotation revealed the final SN-QPL., Results: For the final version of the SN-QPL, 27 items with following four reliable subscales were derived with satisfactory internal consistency: (1) scale SN-QPL-C, "complications and possible postoperative deficits" (n  =  8 items, Cronbach α = 0.88); (2) scale SN-QPL-P, "prognosis and follow-up" (n = 8 items, Cronbach α = 0.86); (3) scale SN-QPL-I, "preoperative inpatient stay and organizational issues" (n = 5 items, Cronbach α = 0.75); and (4) scale SN-QPL-S: "safety of the surgical procedure" (with n = 6 items, Cronbach α = 0.84). The most unmet information needs were found in SN-QPL-P. The item with the greatest unmet information needs was "How much professional experience does my surgeon have?", Conclusions: Our SN-QPL was well-accepted and perceived as helpful by patients awaiting spinal surgeries. It seems to address meaningful items and questions. It could therefore be useful in optimizing pre- and postoperative satisfaction. Further, our study identified many unaddressed questions warranting communication interventions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: An evidence-based emergency department (ED) atrial fibrillation and flutter (AFF) pathway was developed to improve care. The primary objective was to measure rates of new anticoagulation (AC) on ED discharge for AFF patients who were not AC correctly upon presentation., Methods: This is a pre-post evaluation from April to December 2013 measuring the impact of our pathway on rates of new AC and other performance measures in patients with uncomplicated AFF solely managed by emergency physicians. A standardized chart review identified demographics, comorbidities, and ED treatments. The primary outcome was the rate of new AC. Secondary outcomes were ED length of stay (LOS), referrals to AFF clinic, ED revisit rates, and 30-day rates of return visits for congestive heart failure (CHF), stroke, major bleeding, and death., Results: ED AFF patients totalling 301 (129 pre-pathway [PRE]; 172 post-pathway [POST]) were included; baseline demographics were similar between groups. The rates of AC at ED presentation were 18.6% (PRE) and 19.7% (POST). The rates of new AC on ED discharge were 48.6 % PRE (95% confidence interval [CI] 42.1%-55.1%) and 70.2% POST (62.1%-78.3%) (20.6% [p<0.01; 15.1-26.3]). Median ED LOS decreased from 262 to 218 minutes (44 minutes [p<0.03; 36.2-51.8]). Thirty-day rates of ED revisits for CHF decreased from 13.2% to 2.3% (10.9%; p<0.01; 8.1%-13.7%), and rates of other measures were similar., Conclusions: The evidence-based pathway led to an improvement in the rate of patients with new AC upon discharge, a reduction in ED LOS, and decreased revisit rates for CHF.

Background: Based on today's information and communication technologies the open access paradigm has become an important approach for adequately communicating new scientific knowledge., Objectives: Summarizing the present situation for journal transformation. Presenting criteria for adequate transformation as well as a specific approach for it. Describing our exemplary implementation of such a journal transformation., Methods: Studying the respective literature as well as discussing this topic in various discussion groups and meetings (primarily of editors and publishers, but also of authors and readers), with long term experience as editors and /or publishers of scientific publications as prerequisite., Results: There is a clear will, particularly of political and funding organizations, towards open access publishing. In spite of this, there is still a large amount of scientific knowledge, being communicated through subscription-based journals. For successfully transforming such journals into open access, sixteen criteria for a goal-oriented, stepwise, sustainable, and fair transformation are suggested. The Tandem Model as transformation approach is introduced. Our exemplary implementation is done in the Trans-O-MIM project. It is exploring strategies, models and evaluation metrics for journal transformation. As instance the journal Methods of Information in Medicine will apply the Tandem Model from 2017 onwards., Conclusions: Within Trans-O-MIM we will reach at least nine of the sixteen criteria for adequate transformation. It was positive to implement Trans-O-MIM as international research project. After first steps for transforming Methods have successfully been made, challenges will remain, among others, in identifying appropriate incentives for open access publishing in order to support its transformation.

Previous research has claimed that evaluative conditioning (EC) effects may obtain in the absence of perceptual identification of conditioned stimuli (CSs). A recent meta-analysis suggested similar effect sizes for supra- and subliminal CSs, but this was based on a small body of evidence (k = 8 studies; Hofmann, De Houwer, Perugini, Baeyens, & Crombez, 2010). We critically discuss this prior evidence, and then report and discuss 6 experimental studies that investigate EC effects for briefly presented CSs using more stringent methods. Across these studies, we varied CS duration, the presence or absence of masking, the presence or absence of a CS identification check, CS material, and the instructions communicated to participants. EC effects for longer-duration CSs were modulated by attention to the CS-US pairing. Across studies, we were consistently unable to obtain EC for briefly presented CSs. In most studies, this pattern was observed despite above-chance perceptual identification of the CSs. A meta-analysis conducted across the 27 experimental conditions supported the null hypothesis of no EC for perceptually unidentified CSs. We conclude that EC effects for briefly presented and masked CSs are either not robust, are very small, or are limited to specific conditions that remain to be identified (or any combination of these). (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

This experiment investigated social cognition in borderline personality disorder (BPD). We tested whether BPD-patients' evaluations of others were characterized by splitting, dichotomous thinking, or negativity; and whether they showed less complex understanding of others. Participants discussed a problem with three alleged mental health worker trainees, performing three interpersonal roles (rejecting, accepting and neutral). Participants evaluated trainees in a structured response format and in a semi-structured interview. BPD-patients (n = 18) were compared to Cluster-C personality disorder patients (n = 18) and nonpatients (n = 18). From visual analog scales with opposite trait descriptions (structured response format) negativity, dichotomous thinking, and splitting scores were derived. The interviews were scored by an independent rater on affect tone, differentiation, and complexity of attributions. BPD-patients showed, in all conditions, and in both response formats, more dichotomous thinking than control groups. Evidence for splitting as specific BPD-characteristic was not convincing, and more negativity in BPD was only found with the rejecting role and structured responses. The interview-based evaluations by BPD-patients could not be discriminated from nonpatients in cognitive complexity. Results indicate that dichotomous thinking, and not so much splitting, negativity, or less complexity, is central in the interpretation of others by BPD-patients. Treatment might address dichotomous thinking to reduce BPD-patients' interpersonal problems., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In the 19th century, several authors held the view that nightmares are caused by oxygen shortage. The present study was designed to study nightmare frequency in patients with obstructive sleep apnea syndrome and its relationship to respiratory parameters. A brief questionnaire was administered to 323 patients with sleep apnea syndrome before their first laboratory night. The reduction in nightmare frequency in the sleep apnea group was explained by the reduced dream recall frequency. Despite some illustrative examples of a correlation between oxygen desaturation and dream content, the respiratory parameters as measures of sleep apnea syndrome severity did not correlate substantially with nightmare frequency. Psychiatric comorbidity and an intake of psychotropic medication were associated with heightened nightmare frequency in this sample. It must be concluded that the oxygen hypothesis did not play a major role in explaining the occurrence of nightmares. As this might be partly explained by adaptation to the nightly desaturation periods, it will be fruitful to apply experimental procedures that interrupt airflow during (rapid eye movement) REM sleep for short periods in a systematic way without the knowledge of the sleeper and to then study their effects on dream content. Some patients reported a correlation between daytime stressors and nightmares, which is in line with modern etiological models of nightmares.

Purpose: Guanylyl cyclase C (GCC), a receptor for bacterial diarrheagenic enterotoxins, may be a prognostic and predictive marker to detect occult micrometastases in patients undergoing staging for colorectal cancer. However, quantification of GCC expression in tissues by the quantitative reverse transcription-PCR (qRT-PCR) has not undergone analytic and clinicopathologic validation., Experimental Design: A technique to quantify GCC mRNA in tissues employing RT-PCR was developed and validated employing external calibration standards of RNA complementary to GCC., Results: GCC qRT-PCR exhibited reaction efficiencies >92%, coefficients of variations <5%, linearity >6 orders of magnitude, and a limit of quantification of >25 copies of GCC cRNA. This assay confirmed that GCC mRNA was overexpressed by colorectal tumors from 41 patients, which correlated with increased GCC protein quantified by immunohistochemistry. Analyses obtained with 164 lymph nodes from patients free of cancer and 15 nodes harboring metastases established a threshold for metastatic disease of approximately 200 GCC mRNA copies/mug total RNA, with a sensitivity of 93% and specificity of 97%. GCC mRNA above that threshold was detected in 76 of 367 (approximately 21%) nodes free of disease by histopathology from 6 of 23 (26%) patients, suggesting the presence of occult micrometastases., Conclusions: Quantifying GCC mRNA in tissues by RT-PCR employing external calibration standards is analytically robust and reproducible, with high clinicopathologic sensitivity and specificity. This validated assay is being applied to approximately 10,000 lymph nodes in a prospective trial to define the sensitivity of GCC qRT-PCR for staging patients with colorectal cancer.

Guanylyl cyclase C (GC-C), a receptor specifically expressed in cells originating from differentiated intestinal epithelium, is a marker and therapeutic target for colorectal cancer metastases. Intestinal metaplasia, in which epithelial cells assume histological and molecular characteristics of differentiated intestinal enterocytes, is a common precursor to adenocarcinomas of the esophagus and stomach. Thus, those tumors, tissues adjacent to them, and their associated regional lymph nodes were assessed for GC-C expression by reverse transcription coupled with the PCR. GC-C mRNA was detected in five of five and eight of nine esophageal and gastric adenocarcinomas, respectively. Also, GC-C mRNA was detected in three of five and six of seven tissues adjacent to, but not histologically involved in, esophageal and gastric adenocarcinomas, respectively, reflecting molecular changes associated with neoplastic transformation preceding histopathological changes. In contrast, three normal gastric specimens did not express GC-C. Furthermore, GC-C mRNA was detected in 1 of 1 lymph node containing tumor cells by histopathology from a patient with gastric adenocarcinoma and in 3 of 11 lymph nodes, all of which were free of tumor cells by histopathology, from a patient with a gastroesophageal junction tumor. This is the first demonstration that GC-C is ectopically expressed by primary and metastatic adenocarcinomas of the esophagus and stomach and suggests that GC-C may be a sensitive and specific clinical marker and target for adenocarcinomas of the upper gastrointestinal tract.

The reliability of measurements of plasma osmolality is known to be biased by technical artifacts, such as the anticoagulant and the osmometric technique used; the resulting measurement errors therefore may cause errors in interpretation of data. In assessing the potential biasing influence of procedural variables, we found that the temperature at which fresh plasma samples were stored, the duration of storage, and the freezing and thawing of samples appeared to significantly (P < 0.01) affect osmolality values around the narrow physiological range. These factors should be considered in the interpretation of studies on the osmoregulation of vasopressin secretion. In particular, the results suggest that data obtained for any but fresh samples, whether frozen-thawed samples or samples stored at room temperature, are unreliable.

The influence of age on several parameters related to water balance was studied in Wistar rats. Plasma AVP concentration and plasma osmolality were increased at midday in 21-month-old rats as compared with 3- and 4-month-old rats. Daily water intake per 100 g body weight was reduced in 14- and 21-month-old rats as compared with 3- and 4-month-old rats, but total water intake was unaltered. These results suggest that there is a change in water balance in Wistar rats with age. In order to obtain information about the influence of age on daily fluctuations in plasma AVP concentration and osmolality these parameters were determined in 4-month-old Wistar rats sacrificed at 2 h intervals during the day and in 20- and 31-month-old rats sacrificed at 8 h intervals. Plasma AVP concentrations were low during the light period and high during the dark period in 4-month-old rats. The relationship between plasma osmolality and plasma AVP concentration was dependent on the time of day in 4-month-old-rats. Plasma AVP concentrations were higher at 16.00 than at 08.00 and 24.00 in 20-month-old rats, and higher at 24.00 than at 08.00 and 16.00 in 31-month-old rats. In contrast to the plasma AVP concentration during the light period, the average daily AVP concentration (average of plasma AVP concentrations at 08.00, 16.00 and 24.00) was increased in 31-month-old rats only. The relationship between plasma osmolality and plasma AVP concentration was not age-related.(ABSTRACT TRUNCATED AT 250 WORDS)

Severe microbial keratitis developed in a 74-year-old women receiving long-term corticosteroids. Corneal smears revealed slender, fusiform gram-negative bacilli, but the lesion continued to worsen despite intensive antibiotic treatment. After several days, Capnocytophaga sputigena was identified on culture. Specific antimicrobial therapy was instituted, supplemented with corneal cryotherapy. There was gradual clinical improvement. However, a sterile corneal melt led to the late loss of the eye. Although Capnocytophaga are gingival organisms and usually implicated as opportunists in severely ill, neutropenic patients with oral ulcerations, our patient was edentulous and without systemic immunosuppression. An increased awareness of Capnocytophaga is justified because of their widespread antibiotic resistance, capnophilic cultural requirements, and unusual microscopic and cultural morphology.

Complete records from 175 patients with 176 episodes of culture-proven bacterial keratitis treated over a 4-year period at the Massachusetts Eye and Ear Infirmary in Boston were analyzed. Sixty-three percent of the infections involved gram-positive organisms, and 40% involved gram-negative organisms; 15% were polymicrobial. There was a high incidence of infection with Staphylococcus aureus (28%), coagulase-negative staphylococci (14%), diphtheroids (14%), Pseudomonas aeruginosa (14%), and Streptococcus pneumoniae (12%). Gram stain correlation was achieved in 55%. Potential predisposing factors, usually multiple, were identified in 97% of the patients. Fifty percent of the ulcers were associated with such iatrogenic factors as prior topical corticosteroid therapy, penetrating keratoplasty, and contact lens use. Trauma occurred in only 16%. Several statistically significant associations of epidemiologic factors and outcome variables were revealed. Ninety-five percent of the ulcers resolved with therapy, but only 44% of the patients had visual acuity better than the level at admission, and 13% developed major complications.

Eighteen patients with endophthalmitis involving anaerobic bacteria are presented. Endophthalmitis followed cataract surgery in seven patients, penetrating trauma in six, a corneal graft in two, and an infected filtering bleb in two; there was one case of endogenous endophthalmitis. Propionibacterium acnes was the most frequent anaerobe isolated (78% of cases). Thirty-two percent of the patients had polymicrobial infection with mixed aerobic and anaerobic species. Six cases of acute P. acnes endophthalmitis were clinically indistinguishable from other cases of mild to moderately severe endophthalmitis. Four patients presented, after cataract surgery, with chronic, low-grade endophthalmitis of 1 to 15 months' duration, emphasizing that "sterile" endophthalmitis cannot be satisfactory diagnosed clinically. The visual prognosis of treated P. acnes endophthalmitis was often good. Based on principles of anaerobic microbiology, recommendations are made for vitreous collection, transport, and culture.

Intraventricular administration of ACTH1-24 into the rat induced excessive grooming behavior. This response could be blocked by local administration of of neuroleptics into either the nucleus accumbens or the neostriatum. Local administration of [Des-Tyr1]-gamma-endorphine (LPH62-77) but not alpha-endorphin (LPH61-76) in either the nucleus accumbens or the neostriatum mimicked the effect of the neuroleptics. A second intraventricular injection of ACTH1-24 4 h after the first did not cause excessive grooming suggesting the development of acute tolerance. Both haloperidol and DT-gamma-E reduced the development of acute tolerance to ACTH-induced grooming. It is suggested the DT-gamma-E modulates the dopaminergic activity underlying the display of ACTH-induced excessive grooming.

A three-year retrospective study of 36 cases of infectious endophthalmitis seen at a large referral eye center between 1977 and 1980 was conducted. The criterion for infectious endophthalmitis was the culture of microorganisms from aqueous or vitreous on at least two media. The most frequent pathogen was Staphylococcus epidermis; it was isolated from 18 (50%) of the cases. In cases of infectious endophthalmitis following recent cataract extraction, S. epidermidis was isolated from 10 to 17 eyes (58.8%). Complete loss of visual function occurred in 16 of the 36 eyes (44.4%); a visual acuity of 20/400 or better as recorded in 15 eyes (41.6%) and 20/100 or better in eight (22.2%). Fifty percent of the cases were treated with vitrectomy and intraocular antibiotics. Poor visual outcome was associated with gram-negative organisms or delay of vitrectomy more than 24 hours after the initial diagnosis. In cases of postoperative S. epidermidis endophthalmitis, the most favorable visual outcomes were associated with use of intraocular antibiotics and vitrectomy; 80% of cases so treated had a final visual acuity of 20/400 or better and 60% had a visual acuity of 20/100 or better.

In order to investigate the endogenous occurrence of vasopressin fragments that have previously been found to be generated in vitro by brain peptidases and to have highly potent central activity, extracts of hypothalamus, hippocampus and the pituitary gland were fractionated by high pressure liquid chromatography and analyzed by radioimmunoassay systems with different specificities. Substances that were immunologically and chromatographically similar to synthetic C-terminal vasopressin fragments were detected in brain tissue in different amounts, but were virtually absent in the pituitary gland. It is suggested that these components may represent endogenous vasopressin metabolites. The preferential presence in brain supports a selectively central function of these peptides.

Naloxone, haloperidol, and neurotensin suppress ACTH-induced grooming. The suppressive effects of naloxone and of haloperidol on ACTH-induced grooming are observed following subcutaneous as well as intracerebroventricular administration. The suppression of ACTH-induced grooming by these drugs is not accompanied by a change in the relative distribution of grooming elements. From previous data and from the results of the present study it is suggested that the underlying substrate involved in ACTH-induced excessive grooming may differ from that of bombesin-induced grooming.

This study describes effects of various peptides, neurotransmitters and cyclic nucleotides on brain polyphosphoinositide metabolism in vitro. The interconversion of the polyanionic inositol phospholipids was studied by incubation of a lysed crude mitochondrial/synaptosomal fraction with [gamma-32P]-ATP. The reference peptide ACTH1-24 stimulated the formation of radiolabelled phosphatidylinositol 4,5-diphosphate (TPI) and inhibited that of phosphatidic acid (PA). Substance P inhibited both TPI and PA labelling, whereas beta-endorphin inhibited that of PA without any effect on TPI. Morphine had no effect at any concentration tested, whereas high concentrations of naloxone inhibited the labelling of both PA and TPI. Naloxone did not counteract the effects of ACTH1-24. The other peptides tested (lysine 8-vasopressin and angiotensin II) were without any effect. Under the conditions used, adrenaline, noradrenaline and acetylcholine did not affect the labelling of the (poly)phosphoinositides. Both dopamine and serotonin, however, dose-dependently inhibited the formation of radiolabelled TPI and PA. Low concentrations of cAMP stimulated TPI, but higher concentrations had an overall inhibitory effect on the labelling of TPI, PA and especially phosphatidylinositol 4-phosphate (DPI). The cyclic nucleotide did not mediate or counteract the effects of ACTH, and cGMP was without any effect. These results are discussed in the light of current ideas on the mechanism of action of neuropeptides.

mRNA encoding the vasopressin-neurophysin precursor was quantitated in individual hypothalamic nuclei of rats by a liquid hybridization assay. Drinking of 2% saline for 14 days, a treatment that increased the plasma vasopressin concentration 9-fold, resulted in a 5- and 2-fold increase in mRNA levels in the supraoptic and paraventricular nucleus, respectively. This osmotic stimulus had no effect on vasopressin-neurophysin mRNA content of the suprachiasmatic nucleus. This dissociation in regulation of vasopressin-neurophysin mRNA in hypothalamic nuclei indicates the existence of two separate vasopressin systems that are independently activated.

Intracerebroventricular administration of dynorphin-(1-13) inhibits dose-dependently plasma vasopressin level in normal as well as in water-deprived rats, whereas systemic (subcutaneous) administration of this opioid peptide is ineffective in this respect. Simultaneous subcutaneous, but not intracerebroventricular, administration of naloxone prevents the suppressive effect of dynorphin-(1-13) on plasma vasopressin levels.

In rats, ethanol has generally been thought to inhibit vasopressin (VP) release into the peripheral circulation; however, the primary evidence for this conclusion has been indirect. Radioimmunoassay was used to measure VP in the plasma of rats decapitated 5 or 60 min after intraperitoneal injection of ethanol (2.0 g/kg). Confirming the popular notion that ethanol inhibits VP release, VP levels were decreased 60 min after treatment. But radioimmunoassay techniques also revealed that VP release is markedly stimulated shortly after an injection of ethanol.

beta-Endorphin (beta E) exerts a strong inhibitory action on plasma vasopressin (VP) of rats, after intracerebroventricular, but not after subcutaneous injection of the drug. This effect is time- and dose-dependent. Also in the water-deprived rat, this treatment leads to a strong decrease of plasma VP levels. When rats treated with histamine (HIS) intracerebroventricularly to stimulate VP levels are injected with beta E to HIS treatment, beta E partially prevents the increase of plasma VP levels. Naloxone subcutaneously administered, antagonizes the effect of beta E in all the situations we investigated. Opioid receptors, located in the brain as well as in the pituitary, are possibly involved in these processes.