Alcohol Dependence, Co-occurring Conditions and Attributable Burden.

AIMS: Alcohol dependence is associated with high rates of co-occurring disorders which impact health-related quality of life (HRQoL) and add to the cost-of-illness. This study investigated the burden of alcohol dependence and associated co-occurring conditions on health and productivity. METHODS: A cross-sectional survey was conducted in eight European countries. Physicians (Psychiatrists and General Practitioners) completed patient record forms, which included assessment of co-occurring conditions, and patients completed matching self-completion forms. Drinking risk level (DRL) was calculated and the relationship between DRL, co-occurring conditions, work productivity, hospitalisations and rehabilitation stays was explored. RESULTS: Data were collected for 2979 alcohol-dependent patients (mean age 48.8 ± 13.6 years; 70% male). In total, 77% of patients suffered from moderate-to-severe co-occurring psychiatric and/or somatic conditions. High DRL was significantly associated with depression, greater work productivity losses, increased hospitalisations and rehabilitation stays. Co-occurring conditions were significantly associated with poorer HRQoL and decreased work productivity, with a statistical trend towards an increased frequency of rehabilitation stays. CONCLUSIONS: Alcohol-dependent patients manifest high rates of co-occurring psychiatric and somatic conditions, which are associated with impaired work productivity and HRQoL. The continued burden of illness observed in these already-diagnosed patients suggests an unmet need in both primary and secondary care.

Assessment of cannabis use disorders: a systematic review of screening and diagnostic instruments.

BACKGROUND: Cannabis use and misuse have become a public health problem. There is a need for reliable screening and assessment tools to identify harmful cannabis use at an early stage. We conducted a systematic review of published instruments used to screen and assess cannabis use disorders. METHOD: We included papers published until January 2013 from seven different databases, following the PRISMA guidelines and a predetermined set of criteria for article selection. Only tools including a quantification of cannabis use and/or a measurement of the severity of dependence were considered. RESULTS: We identified 34 studies, of which 25 included instruments that met our inclusion criteria: 10 scales to assess cannabis use disorders, seven structured interviews, and eight tools to quantify cannabis use. Both cannabis and substance use scales showed good reliability and were validated in specific populations. Structured interviews were also reliable and showed good validity parameters. Common limitations were inadequate time-frames for screening, lack of brevity, undemonstrated validity for some populations (e.g., psychiatric patients, female gender, adolescents), and lack of relevant information that would enable routine use (e.g., risky use, regular users). Instruments to quantify consumption did not measure grams of the psychoactive compounds, which hampered comparability among different countries or regions where tetrahydrocannabinol concentrations may differ. CONCLUSIONS: Current instruments available for assessing cannabis use disorders need to be further improved. A standard cannabis unit should be studied and existing instruments should be adapted to this standard unit in order to improve cannabis use assessment.

The tangible common denominator of substance use disorders: a reply to commentaries to Rehm et al. (2013a).

In response to our suggestion to define substance use disorders via 'heavy use over time', theoretical and conceptual issues, measurement problems and implications for stigma and clinical practice were raised. With respect to theoretical and conceptual issues, no other criterion has been shown, which would improve the definition. Moreover, heavy use over time is shown to be highly correlated with number of criteria in current DSM-5. Measurement of heavy use over time is simple and while there will be some underestimation or misrepresentation of actual levels in clinical practice, this is not different from the status quo and measurement of current criteria. As regards to stigma, research has shown that a truly dimensional concept can help reduce stigma. In conclusion, 'heavy use over time' as a tangible common denominator should be seriously considered as definition for substance use disorder.

Treatment of bullous pemphigoid with low-dose oral cyclophosphamide: a case series of 20 patients.

BACKGROUND: Cyclophosphamide has been commonly used for the treatment of pemphigus vulgaris and mucous membrane pemphigoid with satisfactory results. Published data of this therapeutic approach for bullous pemphigoid are scant and showed significant morbidity and mortality. OBJECTIVE: To assess the clinical efficacy and safety of low-dose oral cyclophosphamide (CFM) (50-100 mg/day) in patients with refractory bullous pemphigoid. METHODS: We conducted a retrospective study including patients with bullous pemphigoid treated with CFM in the department of Dermatology in the Hospital Clínic of Barcelona, Spain. RESULTS: Complete response was observed in 11 (58%) over 19 evaluable patients. Cyclophosphamide at 50 mg/day was enough to achieve clinical remission in eight of these patients. Partial response was observed in four (21%) more patients. Bone marrow suppression appeared in 12 (60%) patients, but treatment discontinuation was only required in three (15%) cases. Gastrointestinal intolerance occurred in one (5%) patient. One patient died during therapy from heart failure (not attributed to CFM) and another patient developed acute myeloid leukaemia 1.5 years after CFM therapy. CONCLUSIONS: In our series, CFM had a marked therapeutic effect in bullous pemphigoid. These results of efficacy are similar to those described in other autoimmune blistering skin diseases. Only a few patients had to discontinue their treatment due to adverse effects. Therefore, we consider that low-dose oral CFM can be valuable therapeutic alternative in elderly patients with moderate-to-severe bullous pemphigoid.

Mortality of bullous pemphigoid in the first year after diagnosis: a retrospective study in a Spanish medical centre.

BACKGROUND: Prognosis of patients with bullous pemphigoid (BP) is controversial, with a 1-year mortality rate ranging from 6% to 48%. OBJECTIVE: To determine the mortality rate of a large cohort of patients with BP and to identify prognostic factors associated with early mortality. METHODS: Patients diagnosed with BP between January 1, 1990 and December 31, 2010 in a referral unit for blistering skin diseases at a university hospital in Spain were studied retrospectively. Outcome measures were mortality rate during the first year after diagnosis, standardized mortality rate and poor prognostic factors. RESULTS: A total of 101 patients were included in the study. The mean patient age at diagnosis was 77.8 years, and 52 (51.5%) were men. Overall mortality during the first year was 12.9%. We found a standardized mortality ratio of 2.33 [CI95 = (1.25-4.03)]. Advanced age (patient group >80 years old) was the only risk factor for lethal outcome found, with a multivariate risk estimate of 1.09 [CI95 = (1.02-1.16)]. No significant association with mortality was detected for comorbidities, hospitalization history or treatment received for BP. CONCLUSIONS: We found an increased mortality of our BP patients compared with the general population. The mortality rate of BP patients was 2.3 times the expected rate. Observed mortality rate was lower than described in previous European studies. Advanced age impacts the prognosis of patients with BP. Specific treatment for BP appeared not to influence survival.

Defining substance use disorders: do we really need more than heavy use?

AIMS: The aim of the study was to explore whether the concept of heavy substance use over time can be used as definition of substance use disorder. METHODS: Narrative review. RESULTS: Heavy use over time clearly underlies the neurobiological changes associated with current thinking of substance use disorders. In addition, there is evidence that heavy use over time can explain the majority of social problems and of burden of disease (morbidity and mortality). A definition of substance use disorders via heavy use over time would avoid some of the problems of current conceptualizations, for instance the cultural specificity of concepts such as loss of control. Finally, stressing the continuum of use may avoid the high level of stigmatization currently associated with substance use disorders. CONCLUSION: 'Heavy substance use over time' seems to be a definition of substance use disorders in line with results of basic research and epidemiology. Additionally, it reduces stigmatization. This approach should thus be further explored.

The cerebellum and psychological trauma: A systematic review of neuroimaging studies.

Psychological trauma is highly prevalent among psychiatric disorders, however, the relationship between trauma, neurobiology and psychopathology is not yet fully understood. The cerebellum has been recognized as a crucial structure for cognition and emotion, however, it has been relatively ignored in the literature of psychological trauma, as it is not considered as part of the traditional fear neuro-circuitry. The aim of this review is to investigate how psychological trauma affects the cerebellum and to make conclusive remarks on whether the cerebellum forms part of the trauma-affected brain circuitry. A total of 267 unique records were screened and 39 studies were included in the review. Structural cerebellar alterations and aberrant cerebellar activity and connectivity in trauma-exposed individuals were consistently reported across studies. Early-onset of adverse experiences was associated with cerebellar alterations in trauma-exposed individuals. Several studies reported alterations in connectivity between the cerebellum and nodes of large-brain networks, which are implicated in several psychiatric disorders, including the default mode network, the salience network and the central executive network. Also, trauma-exposed individuals showed altered resting state and task based cerebellar connectivity with cortical and subcortical structures that are involved in emotion and fear regulation. Our preferred interpretation of the results is through the lens of the Universal Cerebellar Transform, the hypothesis that the cerebellum, given its homogeneous cytoarchitecture, performs a common computation for motor, cognitive and emotional functions. Therefore, trauma-induced alterations in this computation might set the ground for a variety of psychiatric symptoms.

Simultaneous versus delayed treatment of tobacco dependence in alcohol-dependent outpatients.

INTRODUCTION: There is a high prevalence of smoking among heavy drinkers, which is often forgotten even though it has important health consequences. AIM: To evaluate the effects that providing an intensive tobacco cessation treatment simultaneously with alcohol dependence treatment versus delayed treatment (first alcohol and 6 months later tobacco) has on alcohol and tobacco consumption. METHODS: Ninety-two alcohol-dependent smokers were randomized into either a simultaneous group, in which treatment was given concurrently for quitting both alcohol and tobacco, or a delayed group, in which help to quit smoking was given after 6 months. RESULTS: No differences were found in alcohol abstinence rates in time-to-first relapse or in cumulative abstinence at 6 months. Smoking cessation rates were low overall, but better at 3 months in the simultaneous group, although differences later disappeared. DISCUSSION: Participation in a smoking cessation program does not impair alcohol outcomes, at least during the first 6 months.

Impact of COVID-19 lockdown on individuals under treatment for substance use disorders: Risk factors for adverse mental health outcomes.

BACKGROUND: Individuals with Substance Use Disorders (SUD), are vulnerable to the psychological consequences of the COVID-19 pandemic. This is the first study to assess risk factors of adverse mental health outcomes during lockdown in a SUD population. METHODS: This was a cross-sectional study, conducted through an online survey that was completed by 303 individuals with SUD, attended in the Addiction Unit of University of Barcelona Clínic Hospital. Sociodemographic and clinical data were collected and descriptive analyses were carried out. Depending on whether individuals reported a worsening or no change/improvement in anxiety and depression symptoms during lockdown, the sample was divided in two groups. A logistic regression was then carried out to identify risk factors associated with adverse mental health outcomes. RESULTS: Overall, frequency of use for the majority of individuals with SUD remained stable during lockdown in comparison to the pre-lockdown era, although a reduction was found in frequency of tobacco, alcohol, cannabis and cocaine use in a small fraction of individuals with SUD. Symptoms of clinical anxiety were found in 58.7% of the sample while 48.2% of participants scored above the clinical threshold for depression. In addition, 50.3% of the sample reported a deterioration in depression and anxiety symptoms during lockdown that was associated with the following risk factors: previous trauma-exposure, female gender, distress and isolation, income reduction and alcohol use. CONCLUSION: A high percentage of patients with SUD experienced adverse mental health outcomes during lockdown that were associated with several risk factors, which should be taken into account in policy making and prevention strategies, as well as in clinical practice, in order to provide personalized care to SUD patients during the time of the pandemic.

Cannabis use the week before admission to psychiatric in-patient service as a marker of severity.

OBJECTIVE: To evaluate if cannabis dose recorded as standard joint unit (SJU) consumed before admission and other related factors have an influence on psychiatric inpatient's symptom severity and clinical outcomes. METHODS: Cross-sectional study in an acute psychiatric inpatient unit including 106 individuals. Quantity of cannabis was measured as SJU and symptoms severity through the Brief Psychiatric Rating Scale (BPRS). Secondary outcomes (e.g. length of stay) were also assessed. Bivariate analyses and multivariate analyses were performed to determine the effect of SJU consumed before admission on measures of clinical severity. RESULTS: Point prevalence of cannabis use before admission was 25.5%. Mean BPRS score was 55.8 (SD = 16.1); and 62.9 (SD = 11.1) among cannabis users. A low degree positive correlation between SJU consumed the week before admission and BPRS score (rs = 0.28, p = 0.03) was found. In the multivariate analyses both main diagnostic group, Schizophrenia and other psychotic disorders vs. others (Bipolar and Unipolar Affective Disorders and Addictive disorders) (B = 8.327; 95% CI 4.976-11.677) and need of PRN ("pre re nata" or when necessary) administration of antipsychotics and benzodiazepines (B = 12.13; 95% CI 6.868-17.393) were significant predictors, both increasing BPRS score. CONCLUSIONS: The study did not find a correlation between SJU consumed last week and psychiatric severity. On the other hand, individuals with psychotic disorders reported a higher prevalence of cannabis use the week before admission and displayed higher BPRS scores, which points to the need for the development of tailored interventions for high-risk groups. The SJU is a useful quantification tool suitable for further clinical research.

The blind men and the elephant: Systematic review of systematic reviews of cannabis use related health harms.

Cannabis is the third most used psychoactive substance worldwide. The legal status of cannabis is changing in many Western countries, while we have very limited knowledge of the public health impact of cannabis-related harms. There is a need for a summary of the evidence of harms and risks attributed to cannabis use, in order to inform the definition of cannabis risky use. We have conducted a systematic review of systematic reviews, aiming to define cannabis-related harms. We included systematic reviews published until July 2018 from six different databases and following the PRISMA guidelines. To assess study quality we applied the AMSTAR 2 tool. A total of 44 systematic reviews, including 1,053 different studies, were eligible for inclusion. Harm was categorized in three dimensions: mental health, somatic harm and physical injury (including mortality). Evidence shows a clear association between cannabis use and psychosis, affective disorders, anxiety, sleep disorders, cognitive failures, respiratory adverse events, cancer, cardiovascular outcomes, and gastrointestinal disorders. Moreover, cannabis use is a risk factor for motor vehicle collision, suicidal behavior and partner and child violence. Cannabis use is a risk factor for several medical conditions and negative social consequences. There is still little data on the dose-dependency of these effects; evidence that is essential in order to define, from a public health perspective, what can be considered risky use of cannabis. This definition should be based on quantitative and qualitative criteria that informs and permits the evaluation of current approaches to a regulated cannabis market.

Improving screening and brief intervention activities in primary health care: Secondary analysis of professional accuracy based on the AUDIT-C.

INTRODUCTION AND OBJECTIVE: The ODHIN trial found that training and support and financial reimbursement increased the proportion of patients that were screened and given advice for their heavy drinking in primary health care. However, the impact of these strategies on professional accuracy in delivering screening and brief advice is underresearched and is the focus of this paper. METHOD: From 120 primary health care units (24 in each jurisdiction: Catalonia, England, the Netherlands, Poland, and Sweden), 746 providers participated in the baseline and the 12-week implementation periods. Accuracy was measured in 2 ways: correctness in completing and scoring the screening instrument, AUDIT-C; the proportion of screen-negative patients given advice, and the proportion of screen-positive patients not given advice. Odds ratios of accuracy were calculated for type of profession and for intervention group: training and support, financial reimbursement, and internet-based counselling. RESULTS: Thirty-two of 36 711 questionnaires were incorrectly completed, and 65 of 29 641 screen-negative patients were falsely classified. At baseline, 27% of screen-negative patients were given advice, and 22.5% screen-positive patients were not given advice. These proportions halved during the 12-week implementation period, unaffected by training. Financial reimbursement reduced the proportion of screen-positive patients not given advice (OR = 0.56; 95% CI, 0.31-0.99; P < .05). CONCLUSION: Although the use of AUDIT-C as a screening tool was accurate, a considerable proportion of risky drinkers did not receive advice, which was reduced with financial incentives.

Mismatch negativity impairment associated with alcohol consumption in chronic alcoholics: a scalp current density study.

Previous studies, based on amplitude and latency measurements of auditory event-related brain potentials, yielded inconclusive results about the status of mismatch negativity (MMN) in chronic alcoholics. The present study explores scalp current density (SCD) dynamics during MMN latency range in alcoholics, and correlates electrical SCD results with clinical data of the patients. SCD was computed from 30 electrodes in 16 abstinent chronic alcoholics and 16 healthy control volunteers in a paradigm on MMN elicited by duration changes. Reduced activity was observed in left frontal and right anterior and posterior temporal areas during MMN in alcoholics. Alcohol consumption correlated negatively with SCD intensity in these regions. Delayed activation was observed in the left posterior temporal area in the patients. Alcohol abstinence duration correlated positively with SCD intensity in this region. These results point to an impairment of automatic brain processing mechanisms associated with auditory change detection in chronic alcoholism. The present results suggest a reorganization of the computational neurodynamics of automatic auditory change detection linked to the amount of alcohol consumed in abstinent chronic alcoholics.

Platelet membrane potential as a modulator of aggregating mechanisms.

The membrane potential of platelets suspended in physiological medium and membrane potential changes induced by high potassium concentrations, ouabain and cooling have been measured using a cyanine fluorescent dye (3,3'-dipropylthiodicarbocyanine) [corrected]. The membrane potential of platelets suspended in physiological medium was -63.8 mV. High potassium concentrations, ouabain and cooling induced depolarization of platelet membrane. Depolarization using the above procedures enhanced platelet aggregation induced by ADP, adrenaline and collagen. These results suggest that the membrane potential could modulate platelet activity.

Effects of dihydropyridines and inorganic calcium blockers on aggregation and on intracellular free calcium in platelets.

[Ca2+]i increase is necessary in physiological platelet activity, particularly aggregation and release. The increase of [Ca2+]i observed during platelet activation depends in part on Ca2+ influx from the extracellular medium. The participation of voltage-operated Ca2+ channels as a pathway for Ca2+ entry is controversial. In the present study we have attempted to reinvestigate this problem by measuring aggregation and [Ca2+]i changes in platelets activated by ADP or thrombin and incubated with organic or inorganic blockers of calcium channels. The main findings of the present paper can be summarized as follows: (i) Ni2+, Co2+ and Mn2+, well known inorganic blockers of Ca2+ channels, inhibited platelet aggregation induced by ADP or thrombin in a dose-dependent manner, Ni2+ being the most effective agent. (ii) Thrombin induced a rise in free [Ca2+]i in platelets incubated both in 1 mmol/l Ca(2+)-containing medium and in nominally Ca(2+)-free medium; the rise of free [Ca2+]i was in the first case up to 370 +/- 31 nmol/l and in the second case up to 242 +/- 26 nmol/l, indicating that this observed difference was due to Ca2+ entry from the extracellular medium. Co2+ and Ni2+ abolished that difference by inhibiting Ca2+ influx. (iii) Nisoldipine, nitrendipine and nimodipine (10-50 nmol/l) inhibited in a dose-dependent manner platelet aggregation induced by either ADP or thrombin in platelets incubated in normal-Ca2+ normal-K+ medium, also, aggregation was inhibited to a similar extent in platelets incubated in normal-Ca2+ high-K+ medium. (iv) Nisoldipine--the most effective dihydropyridine to inhibit platelet aggregation--also inhibited Ca2+ influx in platelets incubated in normal-Ca2+ medium, either in normal-K+ or high-K+ media. Our data support the existence of voltage-operated, dihydropyridine-sensitive calcium channels (L-type) and a physiological role for them in platelet function.

Influence of sodium conductances on platelet activation.

The effects of extracellular Na+ and tetrodotoxin on resting membrane potential, cytosolic free Ca2+ levels and aggregation of human platelets have been studied. Neither the decrease in extracellular Na+-concentration (from 140 mmol/l to 0 mmol/l) nor the addition of tetrodotoxin (10(-7) to 10(-5) mol/l) modified the platelet membrane potential. Zero extracellular Na+ concentration or the presence of tetrodotoxin in the medium inhibited platelet aggregation; however, K+-depolarized platelets showed an unchanged aggregation induced by ADP or thrombin in media with zero or low extracellular Na+ concentrations or in the presence of tetrodotoxin. Moreover, zero extracellular Na+ concentration or tetrodotoxin inhibited calcium mobilization in platelets during activation induced by thrombin. Hence, voltage-dependent activation linked to Na+ influx appears to be necessary for ADP- and thrombin-induced platelet aggregation under control conditions. Mechanisms for the role of Na+ conductances in platelet function are discussed.

Who receives treatment for alcohol use disorders in the European Union? A cross-sectional representative study in primary and specialized health care.

BACKGROUND: Alcohol use disorders (AUDs) are highly prevalent in Europe, but only a minority of those affected receive treatment. It is therefore important to identify factors that predict treatment in order to reframe strategies aimed at improving treatment rates. METHODS: Representative cross-sectional study with patients aged 18-64 from primary health care (PC, six European countries, n=8476, data collection 01/13-01/14) and from specialized health care (SC, eight European countries, n=1762, data collection 01/13-03/14). For descriptive purposes, six groups were distinguished, based on type of DSM-IV AUD and treatment setting. Treatment status (yes/no) for any treatment (model 1), and for SC treatment (model 2) were main outcome measures in logistic regression models. RESULTS: AUDs were prevalent in PC (12-month prevalence: 11.8%, 95% confidence interval (CI): 11.2-12.5%), with 17.6% receiving current treatment (95%CI: 15.3-19.9%). There were clear differences between the six groups regarding key variables from all five predictor domains. Prediction of any treatment (model 1) or SC treatment (model 2) was successful with high overall accuracy (both models: 95%), sufficient sensitivity (model 1: 79%/model 2: 76%) and high specificity (both models: 98%). The most predictive single variables were daily drinking level, anxiety, severity of mental distress, and number of inpatient nights during the last 6 months. CONCLUSIONS: Variables from four domains were highly predictive in identifying treatment for AUD, with SC treatment groups showing very high levels of social disintegration, drinking, comorbidity and functional losses. Earlier intervention and formal treatment for AUD in PC should be implemented to reduce these high levels of adverse outcomes.

Identification of Kir2.1 channel activity in cultured trabecular meshwork cells.

PURPOSE: To study the presence of inwardly rectifying K(+) (Kir) channels in cultured bovine (BTM) and human (HTM) trabecular meshwork cells. METHODS: Cultures of BTM and HTM cells were obtained by an extracellular matrix digestion technique. Whole-cell patch-clamp recordings of BTM cells were performed with the appropriate solutions to detect K(+) currents. Also, Western blot analysis of Kir2.1 protein expression was performed on both cultured BTM and HTM cells. RESULTS: A strong inwardly rectifying current at negative potentials to the equilibrium potential for K(+) (E(K+)) and highly selective for K(+) was detected in 60% of cultured BTM cells. The slope conductance of the inward rectification was more pronounced when the extracellular [K(+)] was increased and was proportional to [K(+)](0.45). The current was blocked by Ba(2+) and Cs(+) in a voltage- and concentration-dependent manner, with K(d) at 0 mV, of 74.7 microM and 45.6 mM, respectively. Current amplitude was reduced by increasing extracellular [Ca(2+)]. The current was insensitive to 10 microM glibenclamide and 10 nM tertiapin. The application of 100 microM 8-Br-cAMP reduced the current by 50%. Kir2.1 channel expression was detected in confluent monolayers of BTM and HTM cells by Western blot analysis. CONCLUSIONS: A population of cultured BTM cells expressed an inwardly rectifying K(+) current that illustrates the biophysical and pharmacologic characteristics of the detected Kir2.1 channel protein. Kir2.1 channels are also thought to be present in HTM cells. Kir2.1 channels could be related to TM physiology, because they are involved in contractile and cell volume regulatory responses, two mechanisms that modify TM permeability.

Effects of time of storage, albumin, and osmolality changes on outflow facility (C) of bovine anterior segment in vitro.

PURPOSE: To analyze the influence of time of storage, the presence of albumin at physiological concentrations, and the perfusion with anisosmotic media on the aqueous humor outflow facility (C) of isolated bovine anterior segments (AS). METHODS: Anterior segments dissected from cow eyes were perfused at a constant pressure of 10 mm Hg with Dulbecco's modified Eagle's medium (DMEM; osmolality 300 mOsm/kg), with hyposmotic media (150, 210, and 270 mOsm/kg), or with hyperosmotic media (360, 420, and 480 mOsm/kg). Outflow facility was calculated every 5 seconds as the ratio between average inflow from the reservoir (in microliters per minute) and the perfusion pressure (in millimeters of mercury). Three groups were studied: a 0-hour group, with AS perfused with DMEM 1 to 3 hours after enucleation; a 0-hour alb-group, with AS perfused with DMEM plus 0.1 mg/ml albumin 1 to 3 hours after enucleation; and a 24-hour group, with AS perfused after storage for 24 hours in DMEM. In the 0-hour groups, perfusion with increasingly hyposmotic or hyperosmotic media was also made in 30-minute steps, followed by a return to isosmotic medium for 90 minutes. RESULTS: Perfusion of AS with DMEM for 9 hours caused a progressive increase in C that was statistically significant at 225 minutes in the 0-hour group perfused with DMEM and at 195 minutes in the 24-hour group perfused with DMEM. The 0-hour alb-group perfused with DMEM did not show changes in C throughout the 9-hour perfusion period. Perfusion with increasingly hyposmotic media induced a progressive decrease in C that did not recover on return to isotonic medium. Hyperosmotic media caused a progressive increase in C that returned to control values when isotonic medium was again perfused. CONCLUSIONS: Preservation of tissue for C measurements is best achieved with short storage time (1 to 3 hours). Physiological concentrations of albumin (0.1 mg/ml) prevent development of washout, suggesting that albumin or an albumin-bound factor in aqueous humor may play a role in the maintenance of outflow resistance. Outflow facility also may be influenced by volume changes in the trabecular meshwork.

Sensory receptors in the anterior uvea of the cat's eye. An in vitro study.

PURPOSE: To identify electrophysiologically the functional types of sensory fibers innervating the iris and the ciliary body of the cat's eye. METHODS: The uveal tract tract of cat's eye was excised and placed in a superfusion chamber. Recordings were made from single afferent units of ciliary nerve branches responding to mechanical stimulation of the iridal surface, the ciliary body, and the choroid with a nylon filament or a glass rod. Chemical sensitivity was explored by applying acetic acid, hypertonic NaCl, and bradykinin. Warm (60 degrees C) and cold (4 degrees C) saline and a servocontrolled thermode were used for thermal stimulation. RESULTS: Thirty per cent of the studied population of sensory units (n = 95) were spontaneously active when the recording was started. Approximately 30% of the fibers conducted in the lowest range of the A-delta group; the remaining 70% were C fibers. Sustained mechanical stimulation of the receptive area elicited a tonic response in approximately 60% of the units, and a phasic response in the remaining 40%. Exposure of the receptive field of mechanosensitive fibers to 600 mM NaCl evoked a long-lasting discharge in 50% of the units; application of 1 to 10 mM acetic acid elicited a short discharge in 30% of the fibers, often followed by inactivation. Bradykinin (1 to 100 microMs) produced a long-lasting response in almost 50% of the units. Warming the receptive field recruited 20% of the explored units, whereas 17% were activated by low temperature. CONCLUSIONS: Two main functional types of sensory fibers innervating the iris and the ciliary body were distinguished: (1) mechanoreceptors, corresponding to afferent units sensitive only to mechanical stimuli were generally silent at rest, had relatively higher force thresholds, and discharged phasically in response to long-lasting mechanical stimulation; (2) polymodal nociceptors, which were activated by mechanical as well as by chemical and/or thermal stimuli, usually displayed spontaneous activity, had lower force thresholds, and fired tonically upon sustained mechanical stimulation.