Time Perspective as a Mediator of Depressive Symptoms in Patients with Polycystic Ovary Syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a chronic endocrinopathy characterized by oligo- or anovulation, clinical and/or biochemical markers of hyperandrogenism, and polycystic ovaries, and it is associated with an increased prevalence of depression. Research conducted on psychiatric patients has shown correlations between depression and decreased cognitive function. The aim of this study was to examine the possible mediation of the time perspective (TP) in the development of depressive symptoms in patients with PCOS. METHODS: A study was conducted on 83 patients with PCOS and 65 healthy women. Standardized questionnaires were used to assess depressive symptoms (Beck Depression Inventory-BDI-II) and time perspective (Zimbardo Time Perspective Inventory-ZTPI). RESULTS: Our study revealed an indirect influence of depressive symptoms on PCOS through the positive future time perspective. In the logistic regression model, which included depression and a given time perspective as predictors of PCOS, only the future TP (ß = -0.004, p < 0.003, OR = 1.004, 95% CI [1.001, 1.008]) was significantly independently related to the occurrence of PCOS. CONCLUSIONS: Our result is another argument for the role of psychoeducation and appropriate communication with a patient from the risk group in a way that builds hope and allows to regain influence on life situation.

Melatonin and the Brain-Heart Crosstalk in Neurocritically Ill Patients-From Molecular Action to Clinical Practice.

Brain injury, especially traumatic brain injury (TBI), may induce severe dysfunction of extracerebral organs. Cardiac dysfunction associated with TBI is common and well known as the brain-heart crosstalk, which broadly refers to different cardiac disorders such as cardiac arrhythmias, ischemia, hemodynamic insufficiency, and sudden cardiac death, which corresponds to acute disorders of brain function. TBI-related cardiac dysfunction can both worsen the brain damage and increase the risk of death. TBI-related cardiac disorders have been mainly treated symptomatically. However, the analysis of pathomechanisms of TBI-related cardiac dysfunction has highlighted an important role of melatonin in the prevention and treatment of such disorders. Melatonin is a neurohormone released by the pineal gland. It plays a crucial role in the coordination of the circadian rhythm. Additionally, melatonin possesses strong anti-inflammatory, antioxidative, and antiapoptotic properties and can modulate sympathetic and parasympathetic activities. Melatonin has a protective effect not only on the brain, by attenuating its injury, but on extracranial organs, including the heart. The aim of this study was to analyze the molecular activity of melatonin in terms of TBI-related cardiac disorders. Our article describes the benefits resulting from using melatonin as an adjuvant in protection and treatment of brain injury-induced cardiac dysfunction.

Late application of hyperbaric oxygen therapy during the rehabilitation of a patient with severe cognitive impairment after a traumatic brain injury.

The hyperbaric therapy resulted in the patient's quick recovery and significantly accelerated the recovery after the brain injury.

Population analysis to assess the influence of age and body weight on pharmacokinetics and pharmacodynamics of dexmedetomidine in New Zealand White rabbits.

The purpose of this work was i) to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model of dexmedetomidine (DEX) in New Zealand White rabbits, ii) to investigate the influence of the age and weight of the animals on the model parameters, and iii) to assess the linearity of DEX PKs in the examined dose range. This was a prospective, crossover study, using a total of 18 New Zealand White rabbits. DEX was administered as a single intravenous bolus injection in the doses from 25 to 300 µg kg-1 . Each New Zealand White rabbit was given the same dose of drug in its three developmental stages. To determine the DEX PK, seven blood samples were taken from each animal. The pedal withdrawal reflex was the PD response used to assess the degree of sedation. Nonlinear mixed effects modelling was used for the population PK/PD analysis. The typical value of elimination clearance was 0.061 L min-1 and was 35% higher in younger New Zealand White rabbits compared with older animals. The PK of DEX was linear in the examined concentration range. Age-related changes in sensitivity to DEX were not detected. The results suggest that due to the pharmacokinetics, younger animals will have lower DEX concentrations and a shorter duration of sedation than older animals given the same doses of DEX per kg of body weight.

The influence of the coadministration of the p-glycoprotein modulator elacridar on the pharmacokinetics of lapatinib and its distribution in the brain and cerebrospinal fluid.

Background Lapatinib is a small-molecule tyrosine kinase inhibitor of human epidermal receptor 2 (HER2) and EGFR that has currently been approved for the treatment of HER2-positive advanced and metastatic breast cancer (BC). The ATP-binding cassette (ABC) family of transporters includes P-glycoprotein (P-gp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2), which substantially restrict the penetration of drugs, including chemotherapeutics, through the blood-brain barrier and blood-cerebrospinal fluid barrier. The aim of this study was to investigate the effects of elacridar, an ABCB1 and ABCG2 inhibitor, on the brain and cerebrospinal fluid uptake of lapatinib. Methods Rats were divided into two groups: one group received 5 mg/kg elacridar and 100 mg/kg lapatinib (an experimental group), and the other group received 100 mg/kg lapatinib (a control group). Lapatinib concentrations in the blood plasma (BP), cerebrospinal fluid (CSF) and brain tissue (BT) were measured by liquid chromatography coupled with tandem mass spectrometry. Results Elacridar significantly increased lapatinib penetration into the CSF and BT (Cmax increase of 136.4% and 54.7% and AUC0-∞ increase of 53.7% and 86.5%, respectively). The Cmax of lapatinib in BP was similar in both experimental groups (3057.5 vs. 3257.5 ng/mL, respectively). Conclusion This study showed that elacridar influenced the pharmacokinetics of lapatinib. The inhibition of ABCB1 and ABCG2 transporters by elacridar substantially enhanced the penetration of lapatinib into the CSF and BT. The blocking of protein transporters could become indispensable in the treatment of patients with breast cancer and brain metastases.

Carbon dioxide as a potential danger to medical rescue teams at work - A case study.

Medical rescue teams might be exposed to the risk of accidental poisoning while performing rescue procedures. Exposure to the risk of lethal carbon dioxide (CO2) concentrations is a rare situation. This case study describes rescuing a patient who suffered from sudden cardiac arrest due to accidental CO2 poisoning. The victim was finally evacuated and resuscitated, but the circumstances of the rescue operation point to the need to equip ambulances with carbon dioxide detectors and hermetic oxygen masks. Med Pr 2017;68(1):135-138.

Influence of the Time of Intravenous Administration of Paracetamol on its Pharmacokinetics and Ocular Disposition in Rabbits.

BACKGROUND AND OBJECTIVES: Paracetamol is one of the most common analgesics and antipyretics applied in health care. The aim of the study was to investigate the influence of the time-of-day administration on the paracetamol pharmacokinetics and its penetration into aqueous humour (AH). METHODS: Rabbits were divided into three groups: I-receiving paracetamol at 08.00 h, II-receiving paracetamol at 16.00 h, and III-receiving paracetamol at 24.00 h. Paracetamol was administered intravenously at a single dose of 35 mg/kg. The concentrations of paracetamol and its metabolite (paracetamol glucuronide) in the plasma, as well as in AH were measured with the validated HPLC-UV method. RESULTS: No significant differences in the pharmacokinetic parameters of paracetamol was observed. When the drug was administered at 24.00 h,  elimination half-life (t 1/2kel) of paracetamol glucuronide was longer than when the drug was administered 08.00 h (P = 0.0193). In addition, a statistically significant increase in the paracetamol glucuronide/paracetamol ratio was observed when the drug was administered at 08.00 vs. 16.00 h (P ≤ 0.0001) and 24.00 h (P ≤ 0.0001). CONCLUSIONS: There was no chronobiological effect on the pharmacokinetic parameters of paracetamol.

Emotional processes in patients undergoing coronary artery bypass graft surgeries with extracorporeal circulation in view of selected indicators of the inflammatory condition.

BACKGROUND: The aim of this study was to describe positive and negative emotions in patients undergoing coronary artery bypass graft (CABG) surgeries with extracorporeal circulation and the correlations between emotions and basic indicators of the inflammatory condition: C-reactive protein (CRP) concentration, body temperature, and leukocyte count. MATERIAL/METHODS: Standardized tools were used to select 52 patients (aged 47-63 years, 6 women--11.5% and 46 men--88.5%) without dementia or depression. The Positive and Negative Affect Schedule (PANAS) was used to examine positive affect (PA) and negative affect (NA) and the State-Trait Anxiety Inventory (STAI X1 and X2) was used to examine the anxiety level. The patients underwent CABG surgery according to a common anesthesia protocol and for 5 consecutive days they were observed in the ward, where selected indicators of the inflammatory condition were monitored. RESULTS: A detailed description of the results of examinations of emotions was presented. The patients with low PA-trait level, high NA-trait level, and high anxiety-trait level (STAI X2) exhibited statistically significantly higher body temperatures than the other patients in the postoperative period. The patients with high NA-trait and anxiety-state levels (STAI X1) had statistically significantly lower CRP levels in the postoperative period than the patients with low NA-trait and anxiety-state levels (STAI X1). CONCLUSIONS: Patients undergoing CABG operations express both positive and negative affects. The changes in the inflammatory markers are expressed mostly by CRP concentration. There exist relationships between the result of tests assessing emotions and the markers of the inflammatory condition.

Non-word reading test vs anaesthesia. How do anaesthetised patients decode the contents without referring to the meaning?

BACKGROUND: The aim of this study was to examine the phonological functioning (reading speed and accuracy) of hospital patients under general anaesthesia administered during colonoscopy. METHODS: In this study the 'Latysz' non-word reading test was used to measure the impact of selected anaesthetics on the phonological aspect of language processing (defined as decoding without referring to the meaning) in a group of 22 anaesthetised patients compared to 23 non-anaesthetised patients from university clinics. RESULTS: Compared to the preoperative performance, a decrease in reading accuracy and reading speed was observed only in the Anaesthesia Group - AG (in the subjects aged ≥ 35 years) 1.5 h after the administration of anaesthetics. Postoperatively, the AG were significantly slower and less accurate than the Control Group - CG - after 1.5 h. After 3 h, the AG had regained their baseline values both in reading accuracy and reading speed. During the last assessment session, the AG pronounced 82% of the words correctly, while the CG pronounced 74% correctly. Moreover, subjects aged ≥ 35 years performed worse than younger subjects in their reading accuracy and speed. CONCLUSIONS: The patients who underwent colonoscopy under general anaesthesia manifested impaired phonological functioning shortly after the procedure, both in the speed and accuracy of reading non-words. However, the accuracy problems subsided relatively quickly.

The influence of the time of day on midazolam pharmacokinetics and pharmacodynamics in rabbits.

BACKGROUND: This study evaluates the time-of-day effect on midazolam and 1-OH midazolam pharmacokinetics, and on the sedative pharmacodynamic response in rabbits. Also, circadian fluctuations in rabbits' vital signs, such as the blood pressure, heart rate and body temperature were examined. The water intake was measured in order to confirm the presence of the animals' diurnal activity. The secondary aim involved the comparison of two methods of data analysis: a noncompartmental and a population modeling approach. METHODS: Twelve rabbits were sedated with intravenous midazolam 0.35 mg/kg at four local times: 09.00, 14.00, 18.00 and 22.00 h. Each rabbit served as its own control by being given a single infusion at the four different times of the day on four separate occasions. The values of the monitored physiological parameters were recorded during the experiment and arterial blood samples were collected for midazolam assay. The pedal withdrawal reflex was used as the measurement of the sedation response. Two and one compartmental models were successfully used to describe midazolam and 1-OH midazolam pharmacokinetics. The categorical pharmacodynamic data were described with a logistic model. RESULTS AND CONCLUSIONS: We did not find any time-of-day effects for the pharmacokinetic and pharmacodynamics parameters of midazolam. For 1-OH midazolam, statistically significant time-of-day differences in the apparent volume of distribution and clearance were noticed. They corresponded well with the rabbits' water intake. The noncompartmental and model-based parameters were essentially similar. However, more information can be obtained from the population model and this method should be preferred in chronopharmacokinetic and chronopharmacodynamic studies.

Evaluation of the Trail Making Test and interval timing as measures of cognition in healthy adults: comparisons by age, education, and gender.

BACKGROUND: Human cognitive functioning can be assessed using different methods of testing. Age, level of education, and gender may influence the results of cognitive tests. MATERIAL AND METHODS: The well-known Trail Making Test (TMT), which is often used to measure the frontal lobe function, and the experimental test of Interval Timing (IT) were compared. The methods used in IT included reproduction of auditory and visual stimuli, with the subsequent production of the time intervals of 1-, 2-, 5-, and 7-seconds durations with no pattern. Subjects included 64 healthy adult volunteers aged 18-63 (33 women, 31 men). Comparisons were made based on age, education, and gender. RESULTS: TMT was performed quickly and was influenced by age, education, and gender. All reproduced visual and produced intervals were shortened and the reproduction of auditory stimuli was more complex. Age, education, and gender have more pronounced impact on the cognitive test than on the interval timing test. The reproduction of the short auditory stimuli was more accurate in comparison to other modalities used in the IT test. CONCLUSIONS: The interval timing, when compared to the TMT, offers an interesting possibility of testing. Further studies are necessary to confirm the initial observation.

Psychomotor functions and interval timing in patients receiving intravenous anesthesia for endoscopic procedures: the pilot study.

Introduction. The aim of this study was to evaluate two measures in a cognitive examination: psychomotor function and the perception of time (PT) in patients after intravenous anesthesia for endoscopic procedures. Material and Methods. We tested 23 anesthetized patients (Anesthesia Group, AG) and 17 not anesthetized patients (Control Group, CG). The Dufour Cross-Shaped Apparatus (DA) was used to assess quick reactions. Perception of time (PT) was measured for 1-, 2-, 5-, and 7-second intervals. The tests were performed before the anesthesia was administered and 1.5, 3, and 6 hours after the procedure was completed. Results. The intervals that were generated and the reproduced visual stimuli were shorter than the patterns. The reproduced 1- and 2-second auditory stimuli were longer than the patterns. The remaining reproduced auditory impulses were shorter than the patterns. Conclusions. In anesthetized patients, quick psychomotor reactions and the ability to time intervals are preserved 1.5 h and later after intravenous anesthesia for endoscopy.

The quality of defibrillation performance among students of the University of Medical Sciences.

The major objective was to assess the time period from a witnessed ventricular fibrillation (VF) to the first defibrillation (DEF) in a simulated manikin scenario, while the minor objective was to analyze the most common errors that occurred during DEF and the maintenance of 2-min intervals during resuscitation. We examined 210 students (medical faculty students, MF; and paramedic faculty students, PF) who had to treat a patient with VF. In the study we used the Laerdal(®) Training Manikin and the Zoll M Series(®) defibrillator. The mean time period from the witnessed VF to the first DEF was 50.1 s (SD 32.5 s) in the MF group and 62.9 s (SD 36.9 s) in the PF group (no statistically significant difference). The delay resulted from the lack of constant ECG monitoring and charging in the option "Monitor" instead of the option "Defibrillation." The PF group shortened the 2-min cycles between defibrillations. The problems observed during the study were technical and educational. We concluded that the option "Monitor" should be removed from the equipment because it seems to be redundant. The teaching problems were a lack of constant ECG monitoring, incorrect handling of the defibrillator, and not keeping to 2-min loops of CPR.

Influence of time of day on propofol pharmacokinetics and pharmacodynamics in rabbits.

This study evaluates the administration time-of-day effects on propofol pharmacokinetics and sedative response in rabbits. Nine rabbits were sedated with 5 mg/kg propofol at three local clock times: 10:00, 16:00, and 22:00 h. Each rabbit served as its own control by being given a single infusion at the three different times of day on three separate occasions. Ten arterial blood samples were collected during each clock-time experiment for propofol assay. A two-compartment model was used to describe propofol pharmacokinetics, and the pedal withdrawal reflex was used as the sedation pharmacodynamic response. The categorical data comprising the presence or absence of pedal withdrawal reflex was described by a logistic model. The typical volume of the central compartment equaled 7.67 L and depended on rabbit body weight. The elimination rate constant depended on drug administration time; it was lowest at 10:00 h, highest at 16:00 h, and intermediate at 22:00 h. Delay of the anesthetic effect, with respect to plasma concentrations, was described by the effect compartment, with the rate constant for the distribution to the effector compartment equal to 0.335 min(-1). Drug concentration had a large effect on the probability of anesthesia. The degree of anesthesia was largest at 10:00 h, lowest at 16:00 h, and intermediate at 22:00 h. In summary, both the pharmacokinetics and pharmacodynamics of propofol in rabbits depended on administration time. The developed population approach may be used to assess chronopharmacokinetics and chronopharmacodynamics of medications in animals and humans.

[Effect of the selected parameters on the development of postoperative cognitive dysfunction]. / Wplyw wybranych czynników na wyst powanie pooperacyjnych zaburzen funkcji poznawczych.

BACKGROUND: Surgery and anaesthesia may account for postoperative complications such as cognitive impairment, depression, and delay of convalescence. The purpose of the study was to assess the influence of different risk factors on cognitive performance and emotional state. METHODS: This study included patients received general anaesthesia for various abdominal, urogenital and vascular surgery. All patients were induced with thiopentone and fentanyl. Succinylcholine was used to facilitate endotracheal intubation. Anaesthesia was maintained with sevoflurane, fentanyl and rocuronium. We assessed the effect of duration of anaesthesia, arterial blood oxygenation, body temperature, pain and neoplastic disease on cognitive function, evaluated using the Mini-Mental State Examination (MMSE) questionnaire. RESULTS: Forty-two women and thirty-three men, aged 65-83 years (mean 71.4) were enrolled in the study. Fourteen women and eleven men, aged 67-84 years (mean 74.2) and hospitalized for nonsurgical disease, served as controls. We found a positive correlation between the MMSE test and impaired SaO2 on the first day after surgery, and a negative correlation with the VAS pain score on the 1st and 5th days. The presence of neoplastic disease, body temperature and duration of anaesthesia had no influence on cognitive function. DISCUSSION: The relationship between low arterial oxygenation and cognitive impairment has been described previously, with the deterioration usually being observed in the immediate postoperative period. We could not find any relationship between severity of pain and cognitive function. Perhaps this was because patients did not properly understand the VAS score and could not rate severity o pain properly.

[Iatrogenic tracheal rupture, tension pneumotorax and cardiac arrest]. / Jatrogenny uraz tchawicy powiklany obustronna odma prezna i zatrzymaniem krazenia.

BACKGROUND: Tracheobronchial rupture is a life-threatening complication that may occur during and/or after intubation and tracheostomy. In the majority of described cases, the posterior membranous part of the trachea was affected. CASE REPORT: A 35-year-old woman was admitted to the ICU because of viral meningo-encephalitis with subsequenttetraplegia and respiratory failure. Five days after admission she underwent surgical tracheotomy.The immediate postoperative period was complicated by accidental misplacement of the tracheal tube with hypoxia and bradycardia. The patient was intubated with difficulty and an endotracheal tube was inserted over a bougie guidewire. An ENT surgeon re-inserted the tracheal tube, but two hours later bilateral pneumothorax with subcutaneous emphysema occurred, and the patient was re-intubated. This was followed by a cardiac arrest. CPR was commenced and thoracic drains were inserted, resulting in a return of spontaneous circulation. Bronchoscopy revealed a 1 cm laceration of the anterior tracheal wall. The patient was ventilated for another 50 days and eventually recovered without neurologic deficit. CONCLUSIONS: Tracheal rupture is a rare complication of tracheostomy, and it is difficult to determine the exact mechanism of injury in the case described. In any case of sudden deterioration of a newly tracheotomized patient, pneumothorax should be suspected. Immediate intubation and bronchoscopy are recommended.

Novel competitive PCR methods for quantitation of T-cell receptor delta (TCRD) gene rearrangements.

Since the invention of the polymerase chain reaction (PCR) several quantitative PCR-based approaches have been described. Recently, the real-time PCR method became a standard in quantitative PCR, although high costs of the necessary equipment and reagents make it unaffordable for many laboratories. In this paper we describe two novel competitive PCR techniques, which were used to determine the frequency of T-cell receptor delta gene (TCRD) rearrangements in peripheral blood leukocytes. In the reference gene competitive PCR (rgc-PCR) the rearranged TCRD gene competes with the reference gene (RAG1) for common reagents (dNTPs and Taq polymerase). The intensity ratio of amplification products, TCRD/RAG1, corresponds to the portion of cells containing a rearrangement. A series of reactions was performed, in which RAG1 primers were added to the PCR after different numbers of cycles. On the basis of the number of cycles needed to obtain equal band intensity, the frequency of cells containing a rearrangement was calculated. In the common primer competitive PCR (cpc-PCR), two gene rearrangements, Vdelta1-Jdelta1 and Vdelta2-Jdelta1, compete for the common Jdelta1 primer. The competing genes are amplified from the same genomic DNA template; therefore unlike in the method using the internal competitor, the results are not affected by the quantity or quality of the analysed sample. We showed that the rgc-PCR and cpc-PCR are reliable and give reproducible results. The methods do not require any expensive equipment or reagents, and can be used to determine the frequency of gene rearrangements.