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A letter to the editor is presented in response to the article about the treatment of psychogenic catatonia with lorazepam that was previously published.

Summary: The muscle-sparing thoracotomy offers several benefits over the traditional posterolateral thoracotomy approach for surgically accessing the chest cavity. Some of the potential advantages of preserving the latissimus dorsi and serratus anterior muscles include both functional benefits and potential use of these muscles for future flap reconstruction. Nevertheless, the muscle-sparing thoracotomy technique has traditionally been described with a wide exposure and, as a result, a theoretically higher risk of seroma and hematoma formation due to the increased dead space. The authors propose a new approach to muscle-sparing thoracotomy to avoid the disadvantages of each technique. By defining two subcutaneous anatomical triangles that can be safely lifted without disrupting the latissimus dorsi and serratus anterior muscles' blood supply, this novel approach provides good exposure, preserves muscle flaps for future use, and minimizes dead space. As a result, this novel muscle-sparing thoracotomy technique has the potential to minimize postoperative complications and maximize patient outcomes., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Pharmacists are vital health care providers to patients with heart failure (HF), but their compliance to the HF core measure has not been clearly defined., Objective: The objective of this study was to measure the impact of pharmacist involvement at discharge on compliance with The Joint Commission HF core measure., Methods: This prospective study was conducted at a 361-bed academic teaching institution. A pharmacist performed chart reviews just prior to discharge on adult patients with a preliminary diagnosis of HF (ie, clinical suspicion) to evaluate compliance with the HF core measure. The pharmacist then intervened as needed to ensure compliance. The primary outcome was HF core measure compliance rates with pharmacist involvement at discharge compared to rates during the same 3-month period during the previous year (without pharmacist involvement)., Results: Of 92 patients admitted with clinical suspicion of HF, the pharmacist was able to review 45 patient charts at discharge (49%). The majority of interventions made by the pharmacist were due to medication discrepancies within the discharge instructions found during medication reconciliation. Rates of compliance with the HF core measure did not differ between the period with pharmacist involvement at discharge and the previous period (without pharmacist involvement, P = .39). However, barriers to compliance related to discharge medication documentation, interdisciplinary communication, and manpower were identified through the process., Conclusion: Although pharmacist involvement at discharge did not translate into improved compliance with the HF core measure, systematic barriers to compliance were identified and are currently being addressed.

Genetically-altered mice, lacking functional NK1 receptors (NK1R-/-), express abnormal behaviours that are prominent in Attention Deficit Hyperactivity Disorder: namely, inattentiveness and impulsivity (indicated by their greater % omissions and premature responses in the 5-Choice Serial Reaction-Time Task (5-CSRTT) and locomotor hyperactivity. We investigated how behaviour in the 5-CSRTT is affected by repeated testing and whether the abnormalities expressed by NK1R-/- mice are mimicked by treating wild type mice with a NK1R antagonist (L 733060 or RP 67580; 5 or 10 mg/kg). Repeated testing with a variable (VITI) or fixed, prolonged (LITI) intertrial interval reduced % omissions. Premature responses also declined, but only in NK1R-/- mice, in the VITI test. By contrast, perseveration increased in both genotypes. RP 67580 (10 mg/kg) increased the % omissions in both genotypes in the VITI, an action which cannot be attributed to NK1R antagonism. Neither drug affected perseveration. However, for premature responses, the response profile suggested that the low and high doses of RP 67580 (VITI) and L 733060 (LITI) had opposing effects on this behaviour. We infer that the effect of NK1R antagonists in the 5-CSRTT is confounded by animals' test experience and non-specific drug effects at sites other than NK1R, possibly L-type Ca²⁺(v) channels.

Objectives. To evaluate the adherence rate to prescribed medications in elderly patients 24-48 hours after being discharged from the hospital. Methods. Family medicine residents visited patients over the age of 65 years at their homes one to two days after being discharged from the hospital and documented all the medications that they were taking since coming home from the hospital. The list of medications was later compared to the medications recorded in hospital discharge instructions. Results. Complete data was available for 46 participants. The average patient age was 76 years; 54.4% were women. Only three patients (6.5%) adhered completely to the discharge medication list found in the medical record. Thirty-six patients (78.2%) reported taking at least one additional prescription medication, twenty patients (43.4%) missed at least one prescription medication, twenty patients (43.4%) reported taking the wrong dose of at least one medication, and nineteen patients (41.3%) reported taking medications at an incorrect frequency. Conclusion. The vast majority of elderly patients in our study did not adhere to the medication regimen in the first two days after hospital discharge. Cost-effective improvements to hospital discharge processes are needed to improve adherence and reduce preventable posthospitalization complications.

Introduction: The primary endpoint was to determine whether point-of-care (POC) International Normalization Ratio (INR) testing would increase the percentage of patients in the therapeutic range. The secondary endpoint was to determine how POC Testing (POCT) would affect the time to intervention (the amount of time it took to contact a patient who had an INR outside the therapeutic range and make the appropriate warfarin adjustment)., Methods: Over an 11-month time period, the authors implemented an anticoagulation-focused quality improvement initiative based on the internal medicine resident continuity clinic. The initiative was designed as a single site before and after study., Results: The proportion of INR values within the therapeutic range before the implementation of POCT (predesign phase) was 25%. After the implementation of POCT (postdesign phase), the percentage of therapeutic INR was 50% (P = 0.005). The time to intervention in the predesign phase was 4 days while intervention was accomplished during the same visit that the blood was sampled in the postdesign phase of this study. The number needed to treat was 4 to obtain a therapeutic INR., Conclusion: The results of this quality improvement study showed significant improvement in the percentage of patients who were in the therapeutic range with the use of POCT. Time to intervention was also markedly improved with the addition of POCT. The authors believe that this is the first study showing such results in an internal medicine academic clinic.

Withdrawal from chronic treatment with benzodiazepines is associated with increased neuronal excitability leading to anxiety, aversive effects and increased seizure sensitivity. After repeated withdrawal experiences, seizure sensitivity increases while withdrawal-induced anxiety and aversion decrease. We used autoradiographical methods employing [(3)H]Ro48 8587, a selective ligand for glutamatergic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors, to study withdrawal-induced changes in AMPA receptor binding in areas of the mouse brain postulated to be involved in these responses. Mice were given 21 days treatment with diazepam (15 mg/kg, s.c. in sesame oil) followed by withdrawal (single withdrawal) or three blocks of 7 days treatment interspersed with 3-day periods to allow washout of drug (repeated withdrawal). In keeping with heightened excitability in withdrawal from chronic diazepam treatment, the single withdrawal group showed, 72 h after their final dose of diazepam, increased [(3)H]Ro48 8587 binding in several brain areas associated with emotional responses or seizure activity, including hippocampal subfields, amygdalar and thalamic nuclei and motor cortex. In contrast, the repeated withdrawal group showed no changes in [(3)H]Ro48 8587 binding in any brain area studied. These observations are consistent with up-regulation of AMPA receptor-mediated transmission being important in withdrawal-induced anxiety and aversion but not in increased seizure sensitivity associated with repeated withdrawal. As changes in AMPA receptor subunit expression alter the functionality of the receptor, future studies will address this possibility.

Rationale: Most studies of the effects of caffeine on performance have used regular caffeine consumers who are deprived at test. Thus the reported effects of caffeine could be explained through reversal of caffeine withdrawal., Objectives: To test how preloading deprived caffeine consumers with 0, 1 or 2 mg/kg caffeine altered the subsequent ability of caffeine to modify mood and performance., Methods: Thirty moderate caffeine consumers were given a drink containing 0, 1 or 2 mg/kg caffeine at breakfast followed 60 min later by a second drink containing either 0 or 1 mg/kg caffeine. Performance on a measure of sustained attention and mood were measured before and after each drink., Results: Administration of both 1 and 2 mg/kg caffeine at breakfast decreased reaction time and 1 mg/kg caffeine also increased performance accuracy on the sustained attention (RVIP) task relative to placebo. Both breakfast doses of caffeine also improved rated mental alertness. Similarly, 1 mg/kg caffeine administered 60 min after breakfast decreased reaction time and increased rated mental alertness in the group who had not been given caffeine at breakfast. However, this second dose of caffeine had no effect on subsequent performance or mood in the two groups who had received caffeine at breakfast., Conclusions: Caffeine reliably improved performance on a sustained attention task, and increased rated mental alertness, in moderate caffeine consumers who were tested when caffeine-deprived. However, caffeine had no such effects when consumers were no longer caffeine deprived. These data are consistent with the view that reversal of caffeine withdrawal is a major component of the effects of caffeine on mood and performance.

The ability to manipulate the genetic makeup of organisms by specific targeting of selected genes has provided a novel means of investigating the neurobiological mechanisms underlying drug abuse and dependence. However, as with other techniques, there are a number of potential pitfalls in the use of genetically manipulated animals (usually mice) in behavioural experiments. This review discusses the techniques involved in creating genetically manipulated mice, and points to opportunities and insights into addictive processes provided by the new science, while illustrating some of the potential problems encountered in interpretation of data obtained from such animals. The use of the mouse as an experimental animal also raises some specific problems which limit the usefulness of the technique at present. Examples taken from research into alcohol and psychostimulant abuse and dependence are used to illustrate the usefulness of genetically manipulated animals in addiction research, the problems of interpretation which sometimes arise, and how techniques are being developed to overcome present limitations to this exciting area of research.

A PCR-based protocol for the identification of genetically modified salmon carrying a growth hormone transgene was developed. Several primer pairs were examined, and the primers that gave consistent results were selected to conduct routine testing. Comparison among several DNA extraction procedures, as well as different buffer compositions, led to the adoption of TriZol as the method of choice. Low potassium and high magnesium chloride concentrations were very important in the overall success of the PCR reaction, whereas buffer pH, ranging from 8.3 to 9.2, had little impact on the amplification reaction. The optimal primer annealing temperature was 52 degrees C. Although fish muscle tissues were the primary source for DNA samples, detection of the transgene was also possible in bones, skin, fins, and other organs. No benefits were achieved by the addition of additives such as dimethyl sulfoxide and betaine to the PCR reaction. This optimized PCR method was used to identify all samples tested (61 samples and 17 controls) with 100% accuracy.

Plasminogen activators are serine proteases induced in the brain by electrical activity leading to synaptic remodelling. They are classified into two distinct subtypes, tissue plasminogen activating factor and urokinase plasminogen activating factor (tPA and uPA, respectively), which are both expressed in brain areas thought to be important in learning and memory. Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of tPA and uPA activity, and is expressed in corresponding brain areas. Mice lacking tPA show a deficit in the acquisition of a 15 s differential reinforcement of low rate of responding (DRL15") task relative to their wild types (WTs) under certain conditions. The current set of experiments were designed to investigate further the role of tPA and to extend our knowledge to uPA and PAI-1, using mice with the respective genes deleted (uPA -/- and PAI-1 -/- mice) in the DRL15" task. uPA -/- mice showed no disruption of DRL acquisition, but PAI-1 -/- mice showed a deficit similar to that seen in tPA -/- mice. In an attempt to compensate for this deficit, experiments using a fixed number of reinforcers or a signalled-DRL15" schedule, similar to that used in rat lesion studies of DRL, were performed. tPA -/- mice were able to complete the signalled-DRL task as well as their WTs, and, similarly, PAI-1 -/- mice were able to learn the fixed-number-of-reinforcers-DRL15" schedule and the signalled-DRL schedule. These data indicate that uPA deletion does not affect performance of a standard DRL15" task, whereas deletion of PAI-1 has the same behavioural consequences in these tasks as deletion of tPA. Deficits of both genotypes can be attenuated by providing either external information on completion of the delay or by equalizing the number of reinforcers obtained.

Rationale: The ability of caffeine to condition liking for flavours depends on the caffeine deprivation status of subjects; however, it is not known if a latent liking for a flavour can be acquired in an undeprived state, which subsequently emerges when consumers are caffeine deprived., Objectives: To determine if exposure of undeprived caffeine consumers to a novel drink containing caffeine leads to increased liking for this drink when they are subsequently tested when caffeine-deprived., Methods: In a double-blind placebo controlled study, four groups of 13 moderate caffeine consumers evaluated a novel flavoured drink on 5 days. The test group consumed this drink with 100 mg caffeine when undeprived on days 1-4, and in a deprived state on day 5. Three control groups had the same conditions on all 5 days, with an undeprived group receiving the caffeinated drink, and two deprived groups receiving the drink with caffeine or placebo., Results: The pleasantness of the drink did not change over the 4 training days in the test group, and did not alter when this group was tested when caffeine-deprived. At no stage did these ratings differ between the test and undeprived control groups. Pleasantness increased significantly over the 5 days in the deprived group who received caffeine, and decreased in the deprived group who received placebo., Conclusions: These results suggest that repeated pairing of a novel flavour with the effects of caffeine in subjects who are not caffeine deprived does not lead to an emergent liking for that flavour when subsequently tested caffeine-deprived. However, the pleasantness of the same caffeinated drink increased if it was consumed when caffeine deprived.

Tissue plasminogen activator, tPA, is induced in the brain by electrical activity leading to synaptic remodeling. It is also induced in the prefrontal cortex (PFC) by acute cocaine. We investigated cocaine-induced locomotor activity, the development of sensitisation to cocaine and cocaine self-administration in mice lacking the gene encoding tPA. Mice lacking tPA (tPA knockout mice, tPA-/-) showed normal spontaneous activity, exhibited cocaine-induced locomotor activity at lower doses than wild-type (WT) control mice and showed a greater degree of cocaine-induced locomotor activity following repeated administration. tPA-/- and WT mice did not differ significantly in the time to acquire self-administration of cocaine (20 microg/i.v. infusion) under an FR2 schedule. Following acquisition of this behavior, these groups also did not differ significantly in the rate of cocaine self-administration across the next three sessions. However, WT mice decreased responses on the active lever during signaled periods when reinforcer was not available; in contrast, tPA-/- mice did not. The emission of non-reinforced responses was most marked at the beginning of each 90 min daily session. This pattern of responding was not seen in tPA-/- mice pressing for food under an FR2 schedule of reinforcement. These results suggest that tPA may play a specific role either in retention of information between sessions or in behavioural inhibition in cocaine self-administration., (Copyright 1999 Elsevier Science B.V.)

We have applied a steady-state theory of microdialysis to characterize the diffusion of ethanol through a microdialysis membrane and through rat striatum. Quantitative characterization required measurement of in vitro and in vivo extraction fractions for ethanol and determination of the clearance of ethanol from brain tissue during steady-state perfusion through a microdialysis probe. Extraction fraction of ethanol was determined in vitro by perfusing a known concentration of ethanol through probes immersed in water at 37 degrees C with stirring. The in vitro extraction fraction yielded a probe permeability value of 0.046 +/- 0.004 cm/min that is comparable with an estimate from published measurements for similar dialysis membranes. The in vivo extraction fraction was determined for probes placed in the striatum. Clearance of ethanol and a brain slice concentration profile of ethanol were determined by measurement of the amount of ethanol remaining in the brain tissue during steady-state perfusion of the probe. Steady state was achieved within 10 min after beginning the ethanol perfusion in vivo, and the extraction fraction was not altered by sedation of the rat with pentobarbital. The tissue concentration profile was symmetrical around the probe track, and ethanol was detected 1 mm from the probe. The experimental clearance rate constant value obtained for ethanol (2.0 +/- 0.3 min(-1)) was higher than that expected for removal solely by loss to the blood. The tissue diffusivity for ethanol, Dt, derived from the experimental measurements was 1.2 +/- 0.2 x 10(-5) cm2/sec. This value is greater than expected for interstitial diffusion, suggesting a substantial contribution by transcellular diffusion of ethanol as well. The predicted tissue concentration profile had a higher peak value and did not extend into the tissue (0.5 mm) as much as the experimental profile (1 mm), although there was reasonable agreement between experiment and theory. Our quantitative characterization of the microdialysis behavior of ethanol in brain provides a framework for interpretation of brain microdialysis experiments using ethanol by supplying, inter alia, a means for estimating the ethanol concentration achieved in the tissue volume being sampled by the probe.