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Background Cefuroxime is an antibiotic agent which is widely used in hospitals. Thus, robotic preparation of prefilled ready-to-administer (RTA) cefuroxime 80 mg/ml injections was validated in our pharmacy. The physicochemical stability of these RTA products is a challenge in Centralised IntraVenous Additive Services (CIVAS). Published stability data for concentrated cefuroxime solutions is limited. Cefuroxime solutions of 10 mg/ml and 50 mg/ml, remained stable for 21 days at +5°C and only 16 to 48 hour at 25°C, respectively (Feutry et al. 2015; Gupta, 2003). Purpose To determine the physicochemical stability of cefuroxime 80 mg/ml solution in polypropylene syringes to establish the shelf-life of the product. Material and methods Cefuroxime powders 1.5 g (n=42) were reconstituted with 18 ml of water for injection. The robot added water into vials, solved powder and filled polypropylene syringes. The samples were stored at two different temperatures (4°C and 23°C) and protected from light. Drug concentration, appearance, pH of the solution and amount of degradation products were studied on days 0, 1, 3, 7, 15, 30 and 45. A stability indicating HPLC method for quantitative analysis of cefuroxime was developed and validated. Test for uniformity of dosage units was carried out according to European Pharmacopoeia. Results The concentration of cefuroxime remained over 90% of the initial concentration (Cl 95%) 11 days at 4°C and 2 days at 23°C. No colour change was detected in samples that were stored at 4°C, but slight changes in colour appeared after 24 hours at 23°C. The pH increased from 7.4 to 7.6 during the storage, while the amount of degradation products increased but still stayed under the limit of 3%. Acceptance value for the test for uniformity of dosage units was calculated to be within the acceptance limit. Conclusion Compared to literature data, the physicochemical stability of cefuroxime 80 mg/ml solution stored in the refrigerator was reduced. However, the determined shelf-life of 11 days in the refrigerator enables CIVAS and storage of cefuroxime injections. Storage at room temperature needs to be minimised according to these results. References and/or Acknowledgements 1. Feutry F, et al. Drug Dev Ind Pharm2016;42(1):166–174. 2. Gupta VD. Int J Pharm Compound 2003;7(4):310–312. No conflict of interest

Context: Breakthrough pain is common in patients with cancer and is a significant cause of morbidity in this group of patients. Objectives: The aim of this study was to characterize breakthrough pain in a diverse population of cancer patients. Methods: The study involved 1000 cancer patients from 13 European countries. Patients were screened for breakthrough pain using a recommended diagnostic algorithm and then questioned about the characteristics and management of their pain. Results: Of the 1000 patients, 44% reported incident pain, 41.5% spontaneous pain, and 14.5% a combination. The median number of episodes was three a day. The median time to peak intensity was 10 minutes, with the median for patients with incident pain being five minutes (P < 0.001). The median duration of untreated episodes was 60 minutes, with the median for patients with incident pain being 45 minutes (P = 0.001). Eight hundred six patients stated that pain stopped them doing something, 66 that it sometimes stopped them doing something, and only 107 that it did not interfere with their activities. Patients with incident pain reported more interference with walking ability and normal work, whereas patients with spontaneous pain reported more interference with mood and sleep. As well, 65.5% of patients could identify an intervention that improved their pain (29.5%, pharmacological; 23%, nonpharmacological; 12%, combination). Regarding medications, 980 patients were receiving an opioid to treat their pain, although only 191 patients were receiving a transmucosal fentanyl product licensed for the treatment of breakthrough pain. Conclusion: Breakthrough cancer pain is an extremely heterogeneous condition. © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

In this paper, we proposed a new velocity estimation algorithm for orthogonal frequency division multiplexing (OFDM) systems, which is based on the variance of channel frequency response (CFR) of two adjacent OFDM symbols. The proposed algorithm can fast and accurately estimate the velocity in both Rayleigh and Rician fading channels, and is low in computational complexity and memory storage. Simulation results show that, compared with the conventional crossingbased and covariance-based velocity estimation algorithms, the proposed algorithm can reduce estimation error by nearly 20% on average.

Publisher Summary This chapter describes the different aspects of sea level measuring network in Finland. The water level network that consists of 13 tide gauges was established in the twenties, at which time mareographs were equipped with recording apparatus that recorded the changes of the sea level on paper in the ratio of one to one. The purpose of a control equipment is to ensure, independent of any other system, that the measured data is correct. The equipment consists of an electrode situated in the measuring well, a pulse sensor connected with the electrode, and measuring electronics with a digital display. The observer takes the control measurement once a week by measuring the distance between the tip of the electrode and the reference point situated at the top of the well. The real time measuring system transmits three different messages according to the inter rogation. The data transfer rate is set at 9600 bps and can be changed by the operator. The software of the system takes care of the handshake and answering procedures.

The deformation behaviors of compressed freeze-dried and spray-dried tolbutamide/hydroxypropyl-beta-cyclodextrin molecular dispersions were evaluated and compared with similarly prepared tolbutamides (TBM), hydroxypropyl-beta-cyclodextrins (HP-beta-CD) and as their physical dispersions.TBM, HP-beta-CD, and their 1:1 molecular dispersions were prepared by freeze-drying and spray-drying, and physical dispersions of TBM and HP-beta-CD were blended. Deformation properties of the prepared materials were evaluated by using a compaction simulator and constants derived from Heckel plots. Molecular dynamics (MD) simulations were performed in order to gain a molecular-level view on the deformation behavior of TBM-HP-beta-CD inclusion complex.The freeze-dried TBM polymorphic form II was less prone to overall particle deformation than the spray-dried stable form I. Formation of molecular dispersions decreased the plastic and elastic behaviors of these materials. Also, the MD simulations showed a reduced molecular flexibility of the TBM-HP-beta-CD inclusion complex, as compared to HP-beta-CD.The formation of TBM and HP-beta-CD molecular dispersion resulted in more rigid molecular arrangements, which were less prone to deformation than either HP-beta-CDs or physical dispersions. The results showed how differing molecular, solid, particle, and powder state properties affect the deformation properties of the materials studied.

The role of aerobic capacity (maximal oxygen uptake, VO2max) in connection with chronic low-back pain was assessed in a study mainly designed to evaluate the outcome of inpatient and outpatient treatment of low-back pain. A total of 245 subjects (ages 35-54 years, 71% men)--81 inpatients, 88 outpatients, and 76 controls--who had chronic low-back pain but who were still working, performed maximal graded bicycle ergometer tests four times during the follow-up of 30 months. In every group the estimated VO2max was on the level of the reference values of healthy persons. There were no significant changes in the VO2max in any of the intervention groups during the follow-up period. The correlation analyses showed no connection between aerobic capacity and pain or disability caused by chronic low-back pain. Among several components of physical fitness, aerobic capacity had no predictive value in the course of low-back pain.

In an investigation of the effect of acute heat exposure on aerobic and anaerobic metabolism, eight unacclimated men performed two incremental bicycle ergometer tests in random order, once under thermoneutral conditions (25 degrees C) and once in a hot dry (40 degrees C) environment. Oxygen consumption (VO2) and pulmonary ventilation were measured every minute. Fingertip blood samples were taken at each work level for blood lactate (LA) determination. Compared to the results at 25 degrees C, the mean VO2 was significantly (P less than 0.01) lower during exercise at 40 degrees C. In the hot dry environment the blood lactate threshold was slightly reduced in four subjects, but neither the average peak nor the post-exercise blood LA values differed from the findings at 25 degrees C. During the exercise-heat stress, the ventilatory threshold did not change significantly. The results indicated that, during relatively short-term incremental exercise in a hot environment, almost adequate muscle metabolism can be maintained.

The gas chromatography of all chlorinated methyl acetates, methyl propanoates and methyl mono- and dichlorobutanoates has been studied on Carbowax 20M and SE-30 glass capillary columns under various running conditions. The order of elution on a non-polar column was largely determined by the boiling point of esters, whereas on a polar column it was much influenced by the structure of compounds. Complete separation of the combined mixture of all 27 compounds could not be achieved, however, methyl 3,3-dichlorobutanoate was the only ester overlapped on both columns in spite of the various column temperatures used. The best separation of the mixture was on Carbowax 20M with a temperature program from 50°C at 8°C/min, isothermal running conditions leading either to poor separation of volatile components or long analysis time and broad peaks of higher chlorinated esters. The relative retention times for compounds at the various column temperatures are given and the retention order on a polar and on a non-polar column discussed.

Antigens induced by herpes simplex virus Type 2 (HSV2) were found to be associated with squamous-cell carcinoma in situ of the vulva in nine of 10 patients. The HSV2-induced antigens are DNA-binding proteins that are normally present in the nuclei of infected cells, but in the cells of the carcinomas in situ they were found in the cytoplasm. Whole-virion structural antigens were not present, although there was serologic evidence of previous HSV2 infection in patients tested for the presence of antibodies. The observations reported here and the recent parallel rise in the prevalence of both HSV2 infections and vulvar carcinoma in situ, particularly in women under 40 years of age, suggest an association of HSV2 infection with this type of neoplasia, the nature of which remains to be determined.

Isometric maximal hand grip force was measured with a strain gauge dynamometer in 91 lumberjacks and 31 controls during a 2-min compression-relaxation task. Measurements were carried out on both hands with and without simultaneous vibration exposure. The muscle forces of older subjects were smaller than those of younger men, independent of occupational vibration exposure. The fatigue curves of lumberjacks and control subjects had the same shape. During vibration exposure in the test, the forces diminished in the left hand significantly in the lumberjacks but not in the control subjects. The force level of fatigue curves of the lumberjacks with a history of diminished grip force was lower and decreased more during vibration exposure than in the lumberjacks with a history of normal grip force. The reduction in the hand grip force during vibration exposure in the lumberjacks seemed to be linked to lesions in the peripheral nerves and to activation of a tonic vibration reflex, but probably not to circulation disturbances. The fatigue mechanism seemed to be the same in lumberjacks and control subjects.

Simultaneous determination of aliphatic C2−C20 carboxylic acids and their methyl esters was carried out using SE-30 and OV-351 quartz capillary columns with temperature programming. Complete resolution of all 36 components was achieved. On SE-30 the methyl ester and the corresponding free acid are eluted in turn, whereas on OV-351 acetic acid eluted after methyl octanoate, after which the Cn methyl ester and Cn-6 carboxylic acid (n>9) are eluted one after the other. A non-polar SE-30 column is better for long-chain acids giving sharp peaks without tailing, the analysis time of the mixture being less than 16 minutes. The weight response correction factors for compounds under optimum operating conditions are given.

Gas chromatography of benzene and all chlorobenzenes has been studied on SE-30 and Carbowax 20M glasscapillary columns under various operating conditions. The benzene isomers are eluted on both columns according to their boiling points. Separation of all components in a mixture is achieved on Carbowax 20M, whereas on SE-30 the peaks of closely related isomers overlapped. Also one partial overlapping is observed on a non-polar phase. The relative retention times for compounds are given and the retention order is discussed. The retention behaviour of chlorobenzenes and chlorophenols is compared. By using an SE-30 quartz-capillary column a mixture of 33 individual components gives 29 resolved peaks the analysis time being less than 26 minutes. A polar column proved to be unsuitable for the separation of polychlorophenols.

The gas chromatography of all chlorinated phenols and catechols on a non-polar SE-30 quartz-capillary column has been studied. The relative retention times of the individual components are given and the elution order is discussed. All of the chlorophenols and chlorocatechols can be separated under appropriate operating conditions but simultaneous determination of all the compounds studied resulted in overlapping peaks. Theortho-effect in catechols is stronger than that in phenols. A different order of elution for the compounds studied to that of the corresponding acetate esters is found. Generally, longer retention times for the latter are observed.

Exercise-induced asthma (defined as a fall in PEF of at least 25% of the pre-exercise value) was studied in adult patients with uncomplicated asthma. This was found to occur in 22 out of 52 patients. Pre-exercise inhalation of disodium cromoglycate reduced the mean fall in PEF after maximal exercise from 50% of the pre-exercise value to 23% (open assessment in 11 cases). After submaximal exercise for eight minutes the reduction was from 18% to 10% (double-blind crossover study in 28 cases). It is concluded that disodium cromoglycate partly inhibits the increase of airways resistance after exercise in asthmatic patients.

With several variables, such as patient or subject, disease, surroundings, machine and personnel, it is a wonder that successful epidemiological studies using lung function parameters can be done at all.

The difference in CO2 tension between arterial blood and end-tidal alveolar gas (a-end-tidal)DCO2 was found to correlate fairly well with the VD/VT ratio in 13 healthy subjects and 50 patients with pulmonary diseases (r = 0.74), and to discriminate between healthy subjects and patient groups at least as effectively as did the VD/VT ratio. An increase in breathing frequency from 8 to 32/min, without simultaneous change in alveolar ventilation, was associated with a mean increase in (a-end-tidal) DCO2 of several mmHg in both the healthy subjects and the patient groups. It is concluded that measurement of (a-end-tidal)DCO2 seems to be a clinically useful alternative to measurement of VD/VT ratio for evaluation of the wasted ventilation component, provided that the effect of the breathing frequency on (a-end-tidal) DCO2 is taken into account.

Corrected survival rates for 163 cases of adenocarcinoma of the uterine cervix at 5 and 10 years were 51% and 42%, respectively. For clinical Stages I to IV the 5-year survival rates were 71%, 40%, 30%, and 0%, respectively. The frequency of positive lymph nodes was 4% in Stage I and 71% in Stage II adenocarcinomas. For Stage II this figure is much higher than usually reported in squamous cell carcinoma, and suggests that these tumors behave differently. No significant difference in survival rate was found between pure adenocarcinoma, adenosquamous carcinoma, clear cell adenocarcinoma and adenocarcinoma. Histologic grade showed a direct correlation to the survival rate; for grade I tumors it was about 60%, whereas for patients with grade IV tumors only about 10% survived.

Asbestosis patients have a high cumulative risk of cancer: four of ten asbestosis patients develop cancer. Paraneoplastic involvement of the nervous system, peripheral neuropathy in particular, is often encountered in cancer patients, even at very early stages of the disease. In order to estimate the occurrence of paraneoplastic neuropathy among asbestosis patients, we formed a small cohort (115 asbestosis patients, mean age 56 years, mean duration of exposure to asbestos 21 years) in 1979. Neurological examination revealed slight peripheral neuropathy in 44 (39%) of the patients, 24 (22%) of whom also had central nervous system signs (disturbances in gait and posture, memory and fine movements). The prevalence of peripheral neuropathy among asbestosis patients was higher than among various referent patients (fibrosing alveolitis, diagnosed solvent poisoning and gynaecological carcinoma). No significant differences were found between the patients with and without peripheral neuropathy regarding the following parameters: pulmonary function tests, tumour markers (CEA, ferritin, beta-2-microglobulin), antinuclear antibodies, C3, C4 and circulating immune complexes. Nevertheless, at group level, the asbestosis patients had increased levels of the three tumour markers. Estimates based on the data accumulated so far (10 cancer patients) show that within three years we shall probably have a sufficient number of cancer cases to draw some conclusions about the value of neuropathy in the early diagnosis of occupational cancer.

Two cases of clear cell adenocarcinoma of the vagina detected at follow-up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x-ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen.

The usefulness of an endocervical brush for cytologic sampling was studied in 288 consecutive women attending a colposcopy clinic. One hundred sixty had initial colposcopic examinations with directed biopsies and endocervical curettage (ECC). One hundred twenty-eight had follow-up examinations that included Papanicolaou smears and ECC some time after evaluation and/or treatment for cervical dysplasia. Within an established protocol for the evaluation and management of abnormal Papanicolaou smears, the endocervical brush was compared to ECC. When the combination of colposcopy and cervical conization showed that dysplasia was confined to the endocervix, the endocervical brush was significantly more sensitive than ECC in detecting this endocervical disease (P less than .05). In follow-up evaluations and in patients with unsatisfactory colposcopic examinations, endocervical brush cytology could replace ECC without affecting clinical management. In patients with a satisfactory colposcopic examination, ECC may be required only when endocervical brush cytology is abnormal. Endocervical brush cytology is less costly and painful and could prove to be a reasonable alternative to ECC for the initial evaluation of the endocervix. Endocervical brush cytology shows promise as a safe adjunct to the colposcopic evaluation of pregnant women, whereas ECC is contraindicated in such women.

A group of 115 patients with asbestosis of the lungs was tested in detail for neurological functions and lung functions in order that any possible impaired pulmonary function and neurological signs (especially peripheral neuropathy) could be discovered. Attention was also paid to finding out whether peripheral neuropathy, which is frequently encountered among asbestosis patients, had any role in decreased pulmonary function. A slight trend towards lowered spirometrical values (vital capacity, forced expiratory volume in one second, maximal mid-expiratory flow and maximal expiratory flow at 25% of vital capacity) was found for the group of patients with peripheral neuropathy. No differences in diffusing capacity were found between the groups of patients either with or without peripheral neuropathy. We concluded that the spirometrical findings are more indicative of a parallel phenomenon than a causal factor. Nor was the involvement of the central nervous system associated with decreased pulmonary function. In short, the pulmonary dysfunction of our asbestosis patients did not appreciably contribute to the occurrence of nervous system involvement, whether central or peripheral.

Biopsy specimens taken from eight women with squamous-cell carcinoma in situ of the vulva were studied with transmission electron microscopy for the presence of viral particles. In one of the specimens a 150-nm-diameter viruslike particle was found. The exact nature of this particle was not clear, but it could have represented an immature herpesvirus particle. In seven specimens no evidence of viral particles was detected. These findings provide further evidence that the positivity of vulvar carcinoma in situ for herpesvirus antigen is not due to the presence of whole virus particles.