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The aim of the present study was to evaluate the performance of regional oxygen saturation (rSO2) monitoring with near infrared spectroscopy (NIRS) during pediatric inter-hospital transports and to optimize processing of the electronically stored data. Cerebral (rSO2-C) and abdominal (rSO2-A) NIRS sensors were used during transport in air ambulance and connecting ground ambulance. Data were electronically stored by the monitor during transport, extracted and analyzed off-line after the transport. After removal of all zero and floor effect values, the Savitzky-Golay algorithm of data smoothing was applied on the NIRS-signal. The second order of smoothing polynomial was used and the optimal number of neighboring points for the smoothing procedure was evaluated. NIRS-data from 38 pediatric patients was examined. Reliability, defined as measurements without values of 0 or 15%, was acceptable during transport (> 90% of all measurements). There were, however, individual patients with < 90% reliable measurements during transport, while no patient was found to have < 90% reliable measurements in hospital. Satisfactory noise reduction of the signal, without distortion of the underlying information, was achieved when 20-50 neighbors ("window-size") were used. The use of NIRS for measuring rSO2 in clinical studies during pediatric transport in ground and air-ambulance is feasible but hampered by unreliable values and signal interference. By applying the Savitzky-Golay algorithm, the signal-to-noise ratio was improved and enabled better post-hoc signal evaluation. [ABSTRACT FROM AUTHOR]

To provide retrospective, descriptive information on patients with cervical necrotizing fasciitis treated at a single center during the years 1998-2014, and to evaluate the outcome of a newly introduced treatment strategy. Retrospective analysis of clinical data obtained from medical records. Mortality, pre-morbidity, severity of illness, primary site of infection, type of bacteria, time parameters. The observed 3-month mortality was 6/59 (10 %). The most common initial foci of the infection were pharyngeal, dental or hypopharyngeal. The most common pathogen was Streptococcus milleri bacteria within the Streptococcus anginosus group (66 % of the cases). Using a combined treatment with early surgical debridement combined with hyperbaric oxygen treatment, it is possible to reduce the mortality rate among patients suffering from cervical necrotizing fasciitis, compared to the expected mortality rate and to previous historical reports. Data indicated that early onset of hyperbaric oxygen treatment may have a positive impact on survival rate, but no identifiable factor was found to prognosticate outcome. [ABSTRACT FROM AUTHOR]

Purpose: Thiosulfate may reduce cisplatin-induced ototoxicity, most likely by relieving oxidative stress and by forming inactive platinum complexes. This study aimed to determine the concentration and protective effect of thiosulfate in the cochlea after application of a thiosulfate-containing high viscosity formulation of sodium hyaluronan (HYA gel) to the middle ear prior to i.v. injection of cisplatin in a guinea pig model. Methods: The release of thiosulfate (0.1 M) from HYA gel (0.5% w/w) was explored in vitro. Thiosulfate in the scala tympani perilymph of the cochlea 1 and 3 h after application of thiosulfate in HYA gel to the middle ear was quantified with HPLC and fluorescence detection. Thiosulfate in blood and CSF was also explored. The potential otoprotective effect was evaluated by hair cell count after treatment with thiosulfate in HYA gel applied to the middle ear 3 h prior to cisplatin injection (8 mg/kg b.w.). Results: HYA did not impede the release of thiosulfate. Middle ear administration of thiosulfate in HYA gel gave high concentrations in the scala tympani perilymph while maintaining low levels in blood, and it protected against cisplatin-induced hair cell loss. Conclusion: HYA gel is an effective vehicle for administration of thiosulfate to the middle ear. Local application of a thiosulfate-containing HYA gel reduces the ototoxicity of cisplatin most likely without compromising its antineoplastic effect. This provides a minimally invasive protective treatment that can easily be repeated if necessary. [ABSTRACT FROM AUTHOR]

To evaluate the possibility of using near-infrared spectroscopy (NIRS) to measure tissue oxygenation (StO(2)) during hyperbaric oxygen (HBO) therapy. Nine healthy volunteers (1 female) age 25-37 years, breathed air or oxygen. Tissue oxygenation was measured using NIRS on the thumb. Subjects were blinded to breathing gas. A range of partial pressures of oxygen were administered in 10-min intervals: 21, 101, 21 kPa (compression to 280 kPa), 59, 280, 59 (decompression), 21 kPa. Data were averaged over last 5 min at each pressure. When switching from air to normobaric oxygen (NBO 101 kPa) StO(2) increased from 83% (82-85%, median and interquartile range) to 85% (84-87%) (P < 0.01), while when switching from air at pressure (59 kPa O(2)) to HBO (280 kPa), StO(2) increased from 85% (85-86%) to 88% (87-89%) (P < 0.001). There was no difference between baseline StO(2) while air breathing before NBO or after decompression. Values did not reach the maximal value of 100% at any point. The changes in hemoglobin oxygen saturation in tissue registered by the NIRS monitor when switching from air to oxygen followed inspired PO(2) under normobaric and hyperbaric conditions. [ABSTRACT FROM AUTHOR]

Amphetamine abuse and dependence is a global health concern with a collateral increase in medical and social problems. Although some of the neurobiological mechanisms underlying amphetamine dependence and its devastating effects in humans are known, the development of rational and evidence-based treatment is lagging. There is evidence from preclinical studies suggesting that the endogenous opioid system plays a role in mediating some of the behavioral and neurochemical effects of amphetamine in a variety of controlled settings. In the present study we assessed the effects of naltrexone, an opioid antagonist (50 mg) on the subjective physiological and biochemical response to dexamphetamine (30 mg) in 20 amphetamine-dependent patients. Patients received naltrexone/amphetamine followed by placebo/amphetamine, 1 week apart in a randomized double-blind placebo-controlled design. The primary objective of the study was to evaluate the effect of pretreatment with naltrexone on the subjective response to amphetamine, using a Visual Analog Scale. The secondary objective was to investigate the effects of naltrexone on physiological and biochemical responses to amphetamine, as measured by changes in blood pressure, heart rate, skin conductance, and cortisol. Naltrexone significantly attenuated the subjective effects produced by dexamphetamine in dependent patients (p<0.001). Pretreatment with naltrexone also significantly blocked the craving for dexamphetamine (p<0.001). There was no difference between the groups on the physiological measures. The results suggest that the subjective effects of amphetamine could be modulated via the endogenous opioid system. The potential of naltrexone as an adjunct pharmaceutical for amphetamine dependence is promising.Neuropsychopharmacology (2008) 33, 1856–1863; doi:10.1038/sj.npp.1301572; published online 24 October 2007 [ABSTRACT FROM AUTHOR]

Objective: To determine the workplace concentrations of NO and NO(2) in and around a paediatric incubator during inhaled NO (iNO) treatment and during an accidental emptying of NO cylinders into room air.Design: We simulated iNO-nasal CPAP treatment in order to assess the impact on the occupational environment. Furthermore, two full NO cylinders for therapy, 1,000 ppm, 20 litres, 150 bar and 400 ppm, 10 litres, 150 bar, were emptied as rapidly as possible into an intensive care unit (ICU) room.Setting: University hospital ICU.Measurements and Results: To correctly gauge the contribution from iNO-CPAP we constructed a system measuring breathing zone and room ventilation inlet-outlet values during a 10-ppm iNO treatment of a simulated infant. Maximal breathing zone values were 17.9 +/- 7.0 (mean +/- 95% CI) ppb for NO and 25.2 +/- 4.8 ppb for NO(2). If room inlet values were subtracted, the contributions to breathing zone values emanating from iNO-CPAP were 14.8 +/- 4.6 ppb for NO and 14.6 +/- 4.6 ppb for NO(2). At the ventilation outlet the maximal contributions were 4.2 +/- 2.9 ppb NO and 9.6 +/- 4.3 ppb NO(2). During rapid total release of a gas cylinder in the ICU room, simulating an accident, we found transient NO levels comparable to the high therapeutic dosing range, but only low NO(2) levels.Conclusions: Neither 8-h time-weighted average (TWA) nor 15 min short-term exposure limits (STEL) were exceeded during normal operation or during a simulated accident. The contribution of nitrogen oxides from treatment to workplace air were minor compared to those from ambient air. [ABSTRACT FROM AUTHOR]

Clinical trials of pharmacological agents in stroke have mainly focused on Abstract events that need to be modified in the very acute stage, such as restoration of blood flow with thrombolytic therapy or reducing the effects of ischaemia with neuroprotective therapy. Thrombolytic therapy is, however, only effective within the first few hours of stroke onset and so far, no neuroprotective therapy has proven to be efficacious in humans. Thus, there is a great need for new pharmacological strategies to improve outcome after stroke. Accumulating evidence supports the assumption that the brain is plastic and improvements can be expected after permanent injuries. Acute and chronic alterations in neurotransmitter regulation after injury affects plasticity and may thus provide a basis for new pharmacological targets for stroke recovery. The search for pharmacological therapies that affect the recovery process after a permanent injury has been intensified during the last decade. Amphetamines, in combination with training, are currently one of the most promising pharmacological strategies studied for recovery after stroke. Several non-mutually exclusive hypotheses, more or less supported by experimental studies, have tried to explain the mechanisms underlying the facilitation of recovery of function with amphetamine treatment. Amphetamines are believed to hasten the processes in the brain, such as plasticity mechanisms and resolution of diaschisis. The combination of amphetamine and task-specific training seems to be of importance to the outcome. Results from animal studies are consistent between different models and species, and mainly show an increased rate of recovery but there are a few exceptions, with some studies reporting no effect or even a decreased recovery rate. In humans the number of randomised controlled studies of amphetamines is growing rapidly. Results from a Cochrane systematic review indicate a faster motor and language recovery rate with treatment, but the number of studies is too few and studies are too small to draw definite conclusions about the effect on recovery of stroke. Data in the systematic review also indicate that the mortality rate is higher in amphetamine-treated patients compared with placebo-treated patients. However, this is most likely because of baseline imbalances between the treatment groups with patients with more severe strokes being allocated to amphetamine treatment. Further clinical trials are justified, but at present amphetamines should not be used in clinical practice. 68 [ABSTRACT FROM AUTHOR]

Purpose. To evaluate and compare the ototoxicity and nephrotoxicity of cisplatin and cis-diammineaquachloroplatinum(II) ion (monohydrated complex of cisplatin, MHC, formed in vivo by hydrolysis of cisplatin) after their separate administration to guinea pigs. Methods. A dose of 4 mg/kg body weight of MHC was deemed suitable for the toxicity evaluation after dose titration. Electrophysiological hearing thresholds (auditory brainstem response, ABR), plasma creatinine and weight were measured in three groups of animals before and after receiving MHC 4 mg/kg (0.0141 mmol/kg), cisplatin 4.24 mg/kg (0.0141 mmol/kg, i.e. equimolar dose) or cisplatin 8 mg/kg (0.0267 mmol/kg) as an i.v. bolus injection. Cisplatin and MHC were analysed using liquid chromatography with post-column derivatization. Results. Administration of MHC 4 mg/kg caused a moderate ABR threshold shift, a significant increase in creatinine and a significant weight loss, changes similar to those seen after administration of cisplatin 8 mg/kg. Animals given cisplatin 4.24 mg/kg had a slight increase in creatinine, but had no ABR threshold shift and gained weight during the experiment. The pharmacokinetic parameters of cisplatin and MHC were estimated after administration of cisplatin 4.24 mg/kg and MHC 4 mg/kg. The area under the blood-ultrafiltrate concentration versus time curve (AUC) for cisplatin after administration of MHC 4 mg/kg was 23% (56±5.0 µg·min·ml–1) (means±SD) of that after administration of cisplatin 4.24 mg/kg (240±25 µg·min·ml–1). The AUC for MHC after administration of cisplatin 4.24 mg/kg was 20% (30±4.9 µg·min·ml–1) of that after administration of MHC 4 mg/kg (149±26 µg·min·ml–1). Conclusions. MHC 4 mg/kg causes ototoxicity, nephrotoxicity and weight loss when administered to guinea pigs. The toxic effects were similar to those seen after administration of cisplatin 8 mg/kg and higher than those seen after administration of cisplatin 4.24 mg/kg. [ABSTRACT FROM AUTHOR]

Sixty women with breast cancer (mean age: 61 years; range 36-78 years) were treated with Epirubicin (4'epi-Dox-orubicin), 60 mg m , as single drug therapy. The drug was administered as 2 hours' constant rate infusions. The pharmacokinetics of the drug during the first course of treatment was evaluated by measurements of the plasma concentration of Epirubicin at the end of the infusion period. There was a five-fold inter-individual variation of the dose-normalized maximum plasma concentration, which increased with increasing age of the patients. There was no correlation between this pharmacokinetic parameter and degree of obesity. An increase in maximum plasma concentration was associated with an increasing degree of alopecia ( p = 0.025). Also the degree of nausea and vomiting showed a tendency to increase with increasing maximum plasma concentration ( p = 0.07). Fifty four of the sixty patients entered in the present study were evaluable for clinical response. There was one CR (complete remission). Seventeen patients achieved PR (partial response), and twenty five patients had SD (stable disease). Eleven patients did not respond to treatment. The median maximum plasma concentrations were 322, 316, 336 and 288 ng ml in patients with CR, PR, SD and PD, respectively. The results in the present study showed that 60 mg m of Epirubicin given as a constant rate infusion over 2 hours is a useful alternative to more aggressive combination drug therapy for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of melphalan have been studied after oral doses of 5,10 and 20 mg, and 10 mg i.v. Seven patients with multiple myeloma received the drug on 4 consecutive days and the concentration of melphalan was determined by liquid chromatography. Melphalan was rapidly absorbed after p.o. administration. Absorption lag-time was less than 1 h. The median time for attaining the peak concentration was 1.12 h (97% confidence interval: 0.68-1.55), 1.21 h (0.85-1.43) and 1.08 h (0.84-1.29) after doses of 5,10 and 20 mg. The bioavailability showed large interindividual variations, and was not significantly affected by the dose given. There was a significant decrease in bioavailability during the treatment course ( P < 0.05). Absorption of melphalan obeys first-order kinetics in the dose interval studied. The results indicate that it might be of benefit to administrate oral melphalan for fewer days than the usually used 4 day regimen, in an attempt to achieve a higher bioavailability. [ABSTRACT FROM AUTHOR]

The plasma pharmacokinetics of adriamycin and 4′epi-adriamycin were studied in patients with malignant tumors of the liver after simultaneous regional administration of equal amounts of the two anthracyclines by the arterial route. The use of a highly selective liquid chromatographic analytical method permitted quantification of plasma concentrations of the two drugs as well as their corresponding 13-hydroxy metabolites. The plasma concentrations of each drug followed a three-compartment open model. On average the area under the plasma concentration time curve (AUC) and the maximum plasma concentration ( C ) were 2.1 and 1.7 times larger for adriamycin than for 4′epi-adriamycin, respectively. 4′Epi-adriamycin was eliminated faster than adriamycin, the terminal half-life time being on the average 1.5 times higher for adriamycin. These findings are in agreement with what has previously been observed after intravenous administration. The plasma concentrations of the 13-hydroxy metabolites did not exceed 30 ng ml. The AUC values of these metabolites were on average 20% of the AUC values of the intact drugs. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of adriamycin in patients with malignant tumours of the liver were studied after peripheral intravenous treatment and after regional administration of the drug either by the arterial route or by the portal vein, with or without hepatic artery ligation. The plasma concentration of adriamycin after intravenous as well as after intrahepatic administration followed a three-compartment open model. The results in the present study confirm previous reports of a large inter-individual variation of the pharmacokinetics of adriamycin. After intravenous administration the individual variations in AUC/mg/m and C /mg/m (dose normalized area under plasma concentration time curve and dose normalized maximum plasma concentration, respectively) were more than 5-fold. The area under the plasma concentration time curve (AUC) was on the average 1.5 times higher after the peripheral intravenous administration than after intrahepatic administration. The reduction of maximum plasma concentration ( C ) of adriamycin after intrahepatic administration was even more pronounced than the reduction in AUC (mean value C iv/ C ihep=1.7). The plasma concentration of adriamycinol did not exceed 20 ng/ml. The AUC values of adriamycinol were 20% (median value) of the AUC values of adriamycin, indicating the importance of adriamycinol in the adriamycin therapy. [ABSTRACT FROM AUTHOR]

Cladribine is a newly developed antimetabolite with promising activity in lymphoproliferative disorders. Recent pharmacokinetics investigations have suggested that there is a relationship between its plasma area under the concentration versus time curve (AUC) and the degree of neutropenia posttreatment as well as the therapeutic outcome in hairy-cell leukemia. To enable a simple estimation of the plasma AUC, a limited sampling strategy was developed. Stepwise linear regression was used to determine which were the most important data points for estimation of the plasma AUC after 2-h i.v. infusion, s.c. injection (5 mg/m), and oral administration (10 mg/m) in 27 patients. The most important data points after i.v. infusion in 12 patients were 1, 4, and 24 h, in order of importance. The AUC could be estimated as 2.9081× C5.1851× C20.3265× C.The accuracy and precision (mean value±SD for the determined/estimated AUC was 0.99±0.053) of the model could not be increased by the addition of more data points. A somewhat lower accuracy and precision (0.96± 0.089) was seen with the 2-, 4-, and 24-h data points. These were used to test the regression technique prospectively for the estimation of the AUC after i.v. administration in another set of 10 patients. The accuracy and precision of the estimation of the AUC was similar in this group (1.01±0.109). In all, 11 patients were treated orally (10 mg/m) and 10 patients were treated by s.c. injection (5 mg/m). The most important data points for estimation of the AUC were 2.5, 24, and 0.5 h after oral administration ( AUC=0.8630× C h+ 4.2337× C45.4364× C) and 9, 1, and 16 h after s.c. injection ( AUC=1.8821× C+16.4256× C25.4518× C). The accuracy and precision were 1.01±0.064 after oral dosing and 0.99±0.11 after s.c. injection. The derived mathematical models are reliable for estimation of the plasma AUC of cladribine after 2-h i.v. infusion, oral administration, and s.c. injection. [ABSTRACT FROM AUTHOR]

The binding of anthraquinone glycosides (adriamycin, adriamycinol, daunorubicin, daunorubicinol, and 4′ epiadriamycin) to human serum albumin and human plasma has been studied by equilibrium dialysis. About 62% of adriamycin was bound to human serum albumin (45 g/l). Only minor variations in the degree of binding were observed between the anthraquinone glycosides. The binding degree of adriamycin in plasma from cancer patients was not significantly different from that observed in healthy volunteers, the fraction of free adriamycin being 24.56% ±4.51%, and 27.67%±2.78%, respectively. The plasma albumin concentration was significantly lower in cancer patients than in the healthy volunteers (26.90%±5.88% and 39.24%±1.74%, respectively). In cancer patients the fraction of free adriamycin decreased with increasing plasma albumin concentration. [ABSTRACT FROM AUTHOR]

An earlier whole-body autoradiographic study in mice revealed large differences between the tissue distribution of daunorubicin (D) after administration as free drug as as DNA-linked D. Therefore, the pharmacokinetics of D administered as free drug or linked to DNA was studied in 15 adult patients with acute non-lymphoblastic leukemia. The data obtained following infusion of free drug over either 45 or 240 min could be fitted to a two-compartment open-body model. With the D-DNA infusion considerably higher plasma concentrations were achieved, with a slower distribution and elimination from plasma than seen after the administration of free drug. this confirmed earlier animal data indicating a different pharmacokinetic behavior of D when it was administered linked to DNA. Furthermore, different pharmacokinetic parameters were obtained for D during infusion and in the post-infusion phase after administration of DNA-linked D (P less than 0.005). This finding strongly indicates that the D-DNA acts as a slow-release preparation in humans, which might modify tissue distribution and toxic side-effects of the drug. [ABSTRACT FROM AUTHOR]

The chronopharmacokinetics of 4′epiadriamycin (Epi) have been studied in ten patients with gynecological malignancies. The drug (45 mg m) was administered as a short time (5.0 min) intravenous infusion at 7 a.m. and 7 p.m., in a randomized crossover design. The pharmacokinetics of Epi were evaluated according to the statistical moment theory. Morning and afternoon dosing of Epi was not bioequivalent. The area under the plasma concentration-time curve (AUC), the maximum plasma concentration ( C ), mean residence time (MRT) and the terminal half-life time ( t ) could differ by more than 35% after morning and afternoon dosing. The interindividual variation of AUC and C were larger after morning dosing than after afternoon dosing ( P < 0.04). The morning dose of Epi resulted in higher values of AUC in seven of the ten treated patients as compared to the afternoon dose. The terminal half-life times were shorter in eight of the patients after the morning dose. [ABSTRACT FROM AUTHOR]

The influence of alpha interferon on the plasma pharmacokinetics of epirubicin has been studied in five patients with bronchial cancer. The pharmacokinetic studies of epirubicin (100 mg m) were performed prior to and immediately after a 3 wk period with daily natural alpha interferon treatment (6 × 10 IU i.m.). None of the patients had been treated with antracyclines or interferon prior to entering the present study. The plasma pharmacokinetics of epirubicin were most adequately described by a three compartment open model both prior to and after the interferon treatment. The interferon treatment had no influence on the pharmacokinetics of epirubicin (AUC, C , terminal half life). [ABSTRACT FROM AUTHOR]

The plasma pharmacokinetics of adriamycin after intrapleural administration have been studied. The maximum plasma concentration found after intrapleural instillation of 50 mg was 100 ng ml, the adriamycin half-life being about 2.5 h. Large amounts of the drug are adsorbed from the pleura. Hence risks for cardiomyopathy, previously associated with the repeated intravenous administration of adriamycin, must also be considered after intrapleural administration. [ABSTRACT FROM AUTHOR]

In a human case of plasmacytoma we studied plasma and tumor concentrations of melphalan given intravenously. Intratumoral concentration of melphalan was similar to plasma concentration 60 min after the end of infusion. [ABSTRACT FROM AUTHOR]