Optimal interference of the tibial component of the cementless Oxford Unicompartmental Knee Replacement.

OBJECTIVES: The primary stability of the cementless Oxford Unicompartmental Knee Replacement (OUKR) relies on interference fit (or press fit). Insufficient interference may cause implant loosening, whilst excessive interference could cause bone damage and fracture.The aim of this study was to identify the optimal interference fit by measuring the force required to seat the tibial component of the cementless OUKR (push-in force) and the force required to remove the component (pull-out force). MATERIALS AND METHODS: Six cementless OUKR tibial components were implanted in 12 new slots prepared on blocks of solid polyurethane foam (20 pounds per cubic foot (PCF), Sawbones, Malmo, Sweden) with a range of interference of 0.1 mm to 1.9 mm using a Dartec materials testing machine HC10 (Zwick Ltd, Herefordshire, United Kingdom) . The experiment was repeated with cellular polyurethane foam (15 PCF), which is a more porous analogue for trabecular bone. RESULTS: The push-in force progressively increased with increasing interference. The pull-out force was related in a non-linear fashion to interference, decreasing with higher interference. Compared with the current nominal interference, a lower interference would reduce the push-in forces by up to 45% (p < 0.001 One way ANOVA) ensuring comparable (or improved) pull-out forces (p > 0.05 Bonferroni post hoc test). With the more porous bone analogue, although the forces were lower, the relationship between interference and push-in and pull-out force were similar. CONCLUSIONS: This study suggests that decreasing the interference fit of the tibial component of the cementless OUKR reduces the push-in force and can increase the pull-out force. An optimal interference fit may both improve primary fixation and decrease the risk of fracture.Cite this article: S. Campi, S. J. Mellon, D. Ridley, B. Foulke, C. A. F. Dodd, H. G. Pandit, D. W. Murray. Optimal interference of the tibial component of the cementless Oxford Unicompartmental Knee Replacement. Bone Joint Res 2018;7:226-231. DOI: 10.1302/2046-3758.73.BJR-2017-0193.R1.

Causes and consequences of decreasing atmospheric organic aerosol in the United States.

Exposure to atmospheric particulate matter (PM) exacerbates respiratory and cardiovascular conditions and is a leading source of premature mortality globally. Organic aerosol contributes a significant fraction of PM in the United States. Here, using surface observations between 1990 and 2012, we show that organic carbon has declined dramatically across the entire United States by 25-50%; accounting for more than 30% of the US-wide decline in PM. The decline is in contrast with the increasing organic aerosol due to wildfires and no clear trend in biogenic emissions. By developing a carbonaceous emissions database for the United States, we show that at least two-thirds of the decline in organic aerosol can be explained by changes in anthropogenic emissions, primarily from vehicle emissions and residential fuel burning. We estimate that the decrease in anthropogenic organic aerosol is responsible for averting 180,000 (117,000-389,000) premature deaths between 1990 and 2012. The unexpected decrease in organic aerosol, likely a consequence of the implementation of Clean Air Act Amendments, results in 84,000 (30,000-164,000) more lives saved than anticipated by the EPA between 2000 and 2010.

Correction: Liver AMP-Activated Protein Kinase Is Unnecessary for Gluconeogenesis but Protects Energy State during Nutrient Deprivation.

[This corrects the article DOI: 10.1371/journal.pone.0170382.].

Liver AMP-Activated Protein Kinase Is Unnecessary for Gluconeogenesis but Protects Energy State during Nutrient Deprivation.

AMPK is an energy sensor that protects cellular energy state by attenuating anabolic and promoting catabolic processes. AMPK signaling is purported to regulate hepatic gluconeogenesis and substrate oxidation; coordination of these processes is vital during nutrient deprivation or pathogenic during overnutrition. Here we directly test hepatic AMPK function in regulating metabolic fluxes that converge to produce glucose and energy in vivo. Flux analysis was applied in mice with a liver-specific deletion of AMPK (L-KO) or floxed control littermates to assess rates of hepatic glucose producing and citric acid cycle (CAC) fluxes. Fluxes were assessed in short and long term fasted mice; the latter condition is a nutrient stressor that increases liver AMP/ATP. The flux circuit connecting anaplerosis with gluconeogenesis from the CAC was unaffected by hepatic AMPK deletion in short and long term fasting. Nevertheless, depletion of hepatic ATP was exacerbated in L-KO mice, corresponding to a relative elevation in citrate synthase flux and accumulation of branched-chain amino acid-related metabolites. L-KO mice also had a physiological reduction in flux from glycogen to G6P. These results demonstrate AMPK is unnecessary for maintaining gluconeogenic flux from the CAC yet is critical for stabilizing liver energy state during nutrient deprivation.

Total hip replacement for neck of femur fracture: Comparing outcomes with matched elective cohort.

INTRODUCTION: Current literature suggests that total hip replacement (THR) is superior to hemiarthroplasty (HA) for neck of femur fracture in selected group of patients. The outcomes of THR undertaken for trauma setting remain unclear when comparing with elective THR. We compared the outcomes of THR trauma cohort with best-matched elective cohort. METHODS: We retrospectively reviewed 102 patients that underwent THR due to trauma from 2011 to 2013. We had access to 90 cases with complete records. Another 90 matched elective cases were obtained from local arthroplasty database. The elective cases were matched for gender, surgical approaches, surgeon's grade, types of implant, patient's age at operation date of ±5 years and operation date of ±60days. Subsequently, the selection criteria were relaxed to patient's age at operation date of ±10 years and operation date of ±60days. Unmatched cases were excluded. Complications and death rate were compared. RESULTS: The average age for both cohorts was 70 years. The trauma cohort had statistically significant lower BMI and longer hospital stay (p=0.001). The Functional Comorbidity Index (FCI) and Charlson Age Comorbidity Index (CACI) were the same for both cohorts, reflecting an active patient selection for THR in our centre. The trauma cohort had higher surgical complication rate (9% vs 4%), particularly higher dislocation rate (7% vs 1%); and higher medical complication rate (32% vs 6%). These were consistent with the literature. Contrary to literature, the trauma cohort had six dislocations that five of them were done via anterolateral approach. Among the eight trauma cases with surgical complications, six cases were performed by trainees. The cause of surgical complications remains unclear due to the nature of retrospective study. The trauma cohort had higher death rate than the elective cohort (14% vs 4%), with one post-operative cardiac arrest in the trauma cohort. The rest were non-orthopaedic related deaths, ranging between four months to four years. CONCLUSION: A more robust way of selecting trauma patients for THR is warranted to reduce morbidity and mortality. Follow-up for the trauma cohort is warranted, as the patients are likely to outlive the implants.

Mass spectrometry-based microassay of (2)H and (13)C plasma glucose labeling to quantify liver metabolic fluxes in vivo.

Mouse models designed to examine hepatic metabolism are critical to diabetes and obesity research. Thus, a microscale method to quantitatively assess hepatic glucose and intermediary metabolism in conscious, unrestrained mice was developed. [(13)C3]propionate, [(2)H2]water, and [6,6-(2)H2]glucose isotopes were delivered intravenously in short- (9 h) and long-term-fasted (19 h) C57BL/6J mice. GC-MS and mass isotopomer distribution (MID) analysis were performed on three 40-µl arterial plasma glucose samples obtained during the euglycemic isotopic steady state. Model-based regression of hepatic glucose and citric acid cycle (CAC)-related fluxes was performed using a comprehensive isotopomer model to track carbon and hydrogen atom transitions through the network and thereby simulate the MIDs of measured fragment ions. Glucose-6-phosphate production from glycogen diminished, and endogenous glucose production was exclusively gluconeogenic with prolonged fasting. Gluconeogenic flux from phosphoenolpyruvate (PEP) remained stable, whereas that from glycerol modestly increased from short- to long-term fasting. CAC flux [i.e., citrate synthase (VCS)] was reduced with long-term fasting. Interestingly, anaplerosis and cataplerosis increased with fast duration; accordingly, pyruvate carboxylation and the conversion of oxaloacetate to PEP were severalfold higher than VCS in long-term fasted mice. This method utilizes state-of-the-art in vivo methodology and comprehensive isotopomer modeling to quantify hepatic glucose and intermediary fluxes during physiological stress in mice. The small plasma requirements permit serial sampling without stress and the affirmation of steady-state glucose kinetics. Furthermore, the approach can accommodate a broad range of modeling assumptions, isotope tracers, and measurement inputs without the need to introduce ad hoc mathematical approximations.

Improved performance on cardiopulmonary exercise testing following DDDR pacemaker adjustment: a case report.

We report a case of improved cardiopulmonary exercise (CPX) test outcomes measured 48 h after initial CPX testing and immediately after alterations were made to the settings of a dual chamber, dual sensing pacemaker with exercise detection. The changes allowed successful abdominal surgery to be completed.

5-Aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) effect on glucose production, but not energy metabolism, is independent of hepatic AMPK in vivo.

Metabolic stress, as well as several antidiabetic agents, increases hepatic nucleotide monophosphate (NMP) levels, activates AMP-activated protein kinase (AMPK), and suppresses glucose production. We tested the necessity of hepatic AMPK for the in vivo effects of an acute elevation in NMP on metabolism. 5-Aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR; 8 mg·kg(-1)·min(-1))-euglycemic clamps were performed to elicit an increase in NMP in wild type (α1α2(lox/lox)) and liver-specific AMPK knock-out mice (α1α2(lox/lox) + Albcre) in the presence of fixed glucose. Glucose kinetics were equivalent in 5-h fasted α1α2(lox/lox) and α1α2(lox/lox) + Albcre mice. AMPK was not required for AICAR-mediated suppression of glucose production and increased glucose disappearance. These results demonstrate that AMPK is unnecessary for normal 5-h fasting glucose kinetics and AICAR-mediated inhibition of glucose production. Moreover, plasma fatty acids and triglycerides also decreased independently of hepatic AMPK during AICAR administration. Although the glucoregulatory effects of AICAR were shown to be independent of AMPK, these studies provide in vivo support for the AMPK energy sensor paradigm. AICAR reduced hepatic energy charge by ∼20% in α1α2(lox/lox), which was exacerbated by ∼2-fold in α1α2(lox/lox) + Albcre. This corresponded to a ∼6-fold rise in AMP/ATP in α1α2(lox/lox) + Albcre. Consistent with the effects on adenine nucleotides, maximal mitochondrial respiration was ∼30% lower in α1α2(lox/lox) + Albcre than α1α2(lox/lox) livers. Mitochondrial oxidative phosphorylation efficiency was reduced by 25%. In summary, these results demonstrate that the NMP capacity to inhibit glucose production in vivo is independent of liver AMPK. In contrast, AMPK promotes mitochondrial function and protects against a more precipitous fall in ATP during AICAR administration.

Could exercise be a new strategy to revert some patients with atrial fibrillation?

BACKGROUND: This study is the result of the anecdotal observation that a number of patients with atrial fibrillation (AF) had noted reversion to sinus rhythm (SR) with exercise.We aimed to evaluate the potential role of exercise stress test (EST) for the reversion of AF. METHODS: Patients with AF who were scheduled to undergo electrical cardioversion (DCR) underwent EST using a modified Bruce protocol. RESULTS: Eighteen patients (16 male); aged 36-74 years (mean 58 years) were studied. Five patients (27.7%) had successful reversion with exercise (group 1). Thirteen patients remained in AF (group 2). No patient who failed to revert with exercise did so spontaneously before DCR 3 h to 7 months later (median 20 days). Comparison between group 1 and group 2 did not reveal any significant difference CONCLUSION: This small preliminary study suggests that in some patients it may be possible to revert AF to SR with exercise and avoid DCR and concomitant general anaesthesia. The authors suggest that a larger multicentre randomized trial is warranted to confirm or refute these initial results and if correct identify those who might benefit.

The effect of nicotine in vitro on the integrity of tight junctions in Caco-2 cell monolayers.

Ulcerative colitis is characterised by impairment of the epithelial barrier and tight junction alterations resulting in increased intestinal permeability. UC is less common in smokers with smoking reported to decrease paracellular permeability. The aim of this study was thus to determine the effect of nicotine, the major constituent in cigarettes and its metabolites on the integrity of tight junctions in Caco-2 cell monolayers. The integrity of Caco-2 tight junctions was analysed by measuring the transepithelial electrical resistance (TER) and by tracing the flux of the fluorescent marker fluorescein, after treatment with various concentrations of nicotine or nicotine metabolites over 48 h. TER was significantly higher compared to the control for all concentrations of nicotine 0.01-10 microM at 48 h (p<0.001), and for 0.01 microM (p<0.001) and 0.1 microM and 10 microM nicotine (p < 0.01) at 12 and 24 h. The fluorescein flux results supported those of the TER assay. TER readings for all nicotine metabolites tested were also higher at 24 and 48 h only (p < or = 0.01). Western blot analysis demonstrated that nicotine up-regulated the expression of the tight junction proteins occludin and claudin-1 (p < or = 0.01). Overall, it appears that nicotine and its metabolites, at concentrations corresponding to those reported in the blood of smokers, can significantly improve tight junction integrity, and thus, decrease epithelial gut permeability. We have shown that in vitro, nicotine appears more potent than its metabolites in decreasing epithelial gut permeability. We speculate that this enhanced gut barrier may be the result of increased expression of claudin-1 and occludin proteins, which are associated with the formation of tight junctions. These findings may help explain the mechanism of action of nicotine treatment and indeed smoking in reducing epithelial gut permeability.

First-trimester pregnancy scanning as a screening tool for high-risk and abnormal pregnancies in a district general hospital setting.

This study set out to evaluate the feasibility and acceptability of routine early ultrasound (12-14 weeks) within a district general hospital (DGH) for identifying high-risk and abnormal pregnancies. This was a pilot study for screening by ultrasound examination all women who presented to their community midwife before 12 weeks' gestation. The study involved 991 women who presented clinically pregnant before 12 weeks' gestation between May 1998 and May 1999. Women were offered routinely two ultrasound examinations during their pregnancy, the first at 12-14 weeks' gestation and the second at 20-21 weeks' gestation. The main outcome measures were: range and number of abnormal/high-risk pregnancies identified during an ultrasound scan at 12-14 weeks' gestation; range and number of abnormalities diagnosed during scans at later gestations; outcomes of the pregnancies; questionnaires assessing how the women viewed early pregnancy ultrasound as a method of screening. Nine hundred and eighty-four (99%) women accepted the offer of an early ultrasound scan at 12-14 weeks' gestation; of these 840(85%) women accepted screening for trisomy 21 (T21) by fetal nuchal translucency thickness (NT) and maternal age (fetal medicine foundation risk assessment programme) and this was completed successfully in 797(80%) of cases. Twenty-four women (2%) had a failed pregnancy and where necessary an ERPC was performed following a planned admission. Thirty pregnancies (3%) were diagnosed as abnormal or having high risk of abnormality at the early scan. A major abnormality was confirmed before the expected anomaly scan at 20 weeks in five (17%) pregnancies; all of these patients opted for an elective termination. Twenty-six (3%) pregnancies had a diagnosis of abnormality at their anomaly scan. Of these, three pregnancies were diagnosed as major abnormalities with two resulting in termination of the affected pregnancy before 24 weeks' gestation. Eight hundred and thirty-seven women (85%) completed questionnaires, 833 women (84.5%) were satisfied with the counselling they received before the ultrasound scan and 827 women (84%) answered that they would accept an early pregnancy scan if offered during their next pregnancy. Early pregnancy ultrasound at 12-14 weeks' gestation can be used as an effective method of identifying and screening for major abnormalities of pregnancy within a DGH setting, but it is appropriate to use this in conjunction with an anomaly scan at around 20 weeks' gestation. Women found this method of screening acceptable.

Transcranial Doppler blood flow measurement during cesarean section in two patients with cerebral vascular disease.

We present two cases of neurovascular disease in pregnancy in which transcranial Doppler was used to assess the status of the cerebral circulation during cesarean section under regional anesthesia. One woman had been found to have moyamoya disease, following a series of transient ischemic attacks during her first pregnancy, which ended in spontaneous abortion. On this occasion she was delivered by cesarean section under slowly-induced epidural anesthesia, using ephedrine to maintain the blood pressure, and transcranial Doppler revealed no change in signal in her left middle cerebral artery. Both mother and baby had an uneventful post natal course. The second case involved a primiparous woman with a large arteriovenous malformation that had been detected following generalized seizures, which were treated with valproic acid. Her cesarean section was conducted under spinal anesthesia, and her blood pressure maintained with ephedrine. Again transcranial Doppler revealed no change in signal in her middle cerebral artery during the procedure. We believe this is a potentially useful technique to monitor the cerebral circulation intraoperatively in the presence of cerebrovascular disease.

Differential effects of chronic drug treatment on alpha3* and alpha7 nicotinic receptor binding sites, in hippocampal neurones and SH-SY5Y cells.

1. The aim of this study was to compare the effects of chronic treatment (for 4 or 7 days) with nicotinic drugs and 20 mM KCl on numbers of surface alpha7 nicotinic AChR, identified by [(125)I]-alpha bungarotoxin (alpha-Bgt) binding, in primary hippocampal cultures and SH-SY5Y cells. Numbers of alpha3* nicotinic AChR were also examined in SH-SY5Y cells, using [(3)H]-epibatidine, which is predicted to label the total cellular population of predominantly alpha3beta2* nicotinic AChR under the conditions used. 2. All the nicotinic agonists examined, the antagonists d-tubocurarine and methyllycaconitine, and KCl, upregulated [(125)I]-alpha Bgt binding sites by 20 - 60% in hippocampal neurones and, where examined, SH-SY5Y cells. 3. Upregulation of [(125)I]-alpha-Bgt binding sites by KCl was prevented by co-incubation with the L-type Ca2+ channel blocker verapamil or the Ca2+-calmodulin dependent kinase II (CaM-kinase II) inhibitor KN-62. Upregulation of [(125)I]-alpha-Bgt binding sites by nicotine or 3,[(4-dimethylamino) cinnamylidene] anabaseine maleate (DMAC) was insensitive to these agents. 4. [(3)H]-Epibatidine binding sites in SH-SY5Y cells were not affected by KCl but were upregulated in a verapamil-insensitive manner by nicotine and DMAC. KN-62 itself provoked a 2 fold increase in [(3)H]-epibatidine binding. The inactive analogue KN-04 had no effect, suggesting that CaM-kinase II plays a role in regulating numbers of alpha3* nicotinic AChR. 5. These data indicate that numbers of alpha3* and alpha7 nicotinic AChR are modulated differently. Nicotinic agonists and KCl upregulate alpha7 nicotinic AChR through distinct cellular mechanisms, the latter involving L-type Ca2+ channels and CaM-kinase II. In contrast, alpha3* nicotinic AChR are not upregulated by KCl. This difference may reflect the distinct physiological roles proposed for alpha7 nicotinic AChR.

Informed consent, informed refusal, informed choice--what is it that makes a patient's medical treatment decisions informed?

Informed consent is the fundamental ethical and legal doctrine that protects the patient's rights of personal autonomy and bodily self-determination. An adjunct to the doctrine of informed consent advanced by some is the notion of informed refusal. According to advocates of this concept, incoherent, unconscious, or otherwise incapacitated patients cannot make informed treatment choices because such patients cannot receive a full and current explanation of their health problems and treatment options. This, in turn, raises serious questions about what it is that makes a patient's treatment decisions--whether consents or refusals--informed. Is current, detailed information about the patient's medical condition and treatment options an ethical and legal prerequisite? Can non-medical values and concerns of the patient ever suffice to make the patient's treatment choices informed? How does the concept of informed refusal affect the use of health-care advance directives? This paper will address these important questions.

Solution- and solid-phase synthesis of components for tethered bilayer membranes.

The synthesis of the novel compound PhCH(2)SS(C(24)H(44)N(4)O(10))(C(20)H(41)) (5) for the preparation of tethered bilayer membranes is described. The compound is the all-amide analogue of the previously reported ester-containing membrane-forming material PhCH(2)SS(C(24)H(40)O(14))(C(20)H(41)) (1). The advanced intermediate (C(20)H(41)) C(16)H(28)N(3)O(8) (17) was prepared from the same starting materials using both solution-phase (13% yield) and solid-phase (81% yield) techniques. Monolayers on gold derived from 5 have been analyzed by ellipsometry and FTIR. The monolayers exhibit thicknesses similar to monolayers derived from 1 and possess H-bonded amide functionality.

The metabolism of norethandrolone in the horse: characterization of 16-, 20- and 21-oxygenated metabolites by gas chromatography/mass spectrometry.

After oral administration to a thoroughbred gelding, the anabolic steroid norethandrolone was converted into a complex mixture of oxygenated metabolites. These metabolites were extracted from the urine, deconjugated by methanolysis and converted to their O-methyloxime trimethylsilyl derivatives. Gas chromatographic/mass spectrometric analysis indicated the major metabolites to be 19-norpregnane-3,16,17-triols, 19-norpregnane-3,17,20-triols and 3,17-dihydroxy-19-norpregnan-21-oic acids. Some minor metabolites were also detected.

Metabolism of methandrostenolone in the horse: a gas chromatographic-mass spectrometric investigation of phase I and phase II metabolism.

The phase I and phase II metabolism of the anabolic steroid methandrostenolone was investigated following oral administration to a standardbred gelding. In the phase I study, metabolites were isolated from the urine by solid-phase extraction, deconjugated by acid catalysed methanolysis and converted to their O-methyloxime trimethylsilyl derivatives. GC-MS analysis indicated the major metabolic processes to be sequential reduction of the A-ring and hydroxylation at C6 and C16. In the phase II study, unconjugated, beta-glucuronidated and sulfated metabolites were fractionated and deconjugated using a combination of liquid-liquid extraction, enzyme hydrolysis, solid-phase extraction and acid catalysed methanolysis. Derivatization followed by GC-MS analysis revealed extensive conjugation to both glucuronic and sulfuric acids, with only a small proportion of metabolites occurring in unconjugated form.

The utilitarian core hypothesis: cases for testing the stability of languages in the wake of conquest.

Based on the "utilitarian core hypothesis" that the most common words of a language develop early and resist change, the current exploratory study examined three test cases to suggest what happens to the common core of a language when its speakers are conquered. Whissell (1998) raised this issue by implication through demonstrating that the common core of English is largely Anglo-Saxon and thus survived the Norman Conquest. The notion that unique merits of English accounted for its success has a long history dating at least to Verstegan (1605/1976). We suggested that there are also instances of conquest in history illustrating the persistence of other languages despite the political subjugation of their speakers. Test cases included, in addition to the Norman Conquest of England, the Arab-Berber Conquest of most of the Iberian Peninsula, and Russian domination of modern Uzbekistan. The combined results suggest that persistence of a utilitarian core despite conquest is not an isolated instance. As a phenomenon it offers a more parsimonious account than do appeals to the special merits of English, Spanish, or Modern Uzbek. We have integrated these findings within a psychological framework pertaining to language use and change.

The effects of nicotine on neural pathways implicated in depression: a factor in nicotine addiction?

The prevalence of tobacco smoking varies considerably between different groups within the community, tobacco smoking being particularly prevalent in patients with depressive disorder. This review will focus on results, derived from animal studies, which suggest that, in addition to its primary reinforcing properties, nicotine also exerts effects in stressful environments, which may account for its enhanced addictive potential in depressed patients. It focuses on the evidence that depression sensitises patients to the adverse effects of stressful stimuli, and that this can be relieved by drugs that stimulate dopamine release in the forebrain. This mechanism, it is proposed, contributes to the increased craving to smoke in abstinent smokers exposed to such stimuli, because they become conditioned to use this property of nicotine to produce rapid alleviation of the adverse effects of the stress. The review also explores the possibility that chronic exposure to nicotine elicits changes in 5-HT formation and release in the hippocampus which are depressogenic. It is postulated that smokers are protected from the consequences of these changes, while they continue to smoke, by the antidepressant properties of nicotine. However, they contribute to the symptoms of depression experienced by many smokers when they first quit the habit.

Synthesis and evaluation of [123I]labelled analogues of the partial inverse agonist Ro 15-4513 for the study of diazepam-insensitive benzodiazepine receptors.

The imidazobenzodiazepines ethyl 8-iodo-5,6 dihydro-5-methyl-6-oxo-4H-imidazo[1,5a][1,4] benzodiazepine-3-carboxylate 1 and tert-butyl 8-iodo-5,6 dihydro-5-methyl-6-oxo-4H-imidazo [1,5a][1,4] benzodiazepine-3-carboxylate 2 were prepared to study the diazepam-insensitive (DI) benzodiazepine receptor (BZR) subtype. The [123I] analogues were prepared via iododestannylation reactions in radiochemical yields of 70-80% and a specific activity >2,500 Ci/mmol. The tert-butyl analogue [123I]-2 exhibited nanomolar affinity for BZRs in homogenate membranes of rat cerebellum with Kd values for the diazepam-sensitive (DS) and DI receptors of 3.18 +/- 0.58 and 13.55 +/- 2.72 nM, respectively. The Bmax for cerebellar DS and DI receptors were 1,276 +/- 195 and 518 +/- 26 fmol/mg protein, respectively.