New detection schemes in liquid chromatography

A micropolarimeter interfaced to a liquid chromatograph is shown to be suitable for selective monitoring of the optically-active components in complex samples. When an optically-active eluent is used, indirect determination of even optically-inactive materials is possible, down to the level of 10 ng of an injected component. If a second chromatogram is obtained using the racemic analogue of the optically-active eluent, quantitation can be achieved without standards and without prior analyte identification. This concept is also applicable to the refractive index detector, the absorption detector and the conductivity detector in the special case of ion chromatography, and the ultrasonic detector in gas chromatography.     

Leg-length discrepancy and associated risk factors after paediatric femur shaft fracture: a multicentre study

PurposeThis study was performed to investigate leg-length discrepancy (LLD) and associated risk factors after paediatric femur shaft fractures.MethodsA total of 72 consecutive patients under 13 years old (mean age 6.7 years; 48 boys, 24 girls) with unilateral femur shaft fracture, and a minimum follow-up of 18 months, were included. The amount of LLD was calculated by subtracting the length of the uninjured from that of the injured limb. Risk factors for an LLD ≥ 1 cm and ≥ 2 cm were analyzed using multivariable logistic regression analysis.ResultsHip spica casting, titanium elastic nailing and plating were performed on 22, 40 and ten patients, respectively. The mean LLD was 7.8 mm (sd 8.8) and 29 (40.3%) had a LLD of ≥ 1 cm, while nine (12.5%) had a LLD of ≥ 2 cm. There were significant differences in fracture stability (p = 0.005) and treatment methods (p = 0.011) between patients with LLD < 1 cm and ≥ 1 cm. There were significant differences in fracture site shortening (p < 0.001) and LLD (p < 0.001) between patients with length-stable and length-unstable fractures. Fracture stability was the only factor associated with LLD ≥ 1 cm (odds ratio of 4.0; p = 0.020) in the multivariable analysis.ConclusionThis study demonstrated that fracture stability was significantly associated with LLD after paediatric femur shaft fractures. Therefore, the surgeon should consider the possibility of LLD after length-stable femur shaft fracture in children.Level of EvidencePrognostic level III     

Effects of Acute and Chronic Inflammation on the Pharmacokinetics of Prednisolone in Rats

The effects of acute and chronic stages of carrageenan-induced air-pouch inflammation on the pharmacokinetics of prednisolone were studied in male Wistar rats. Chronic inflammation produced a significant increase in the area under the curve (AUC) of prednisolone compared to control animals (6594 ± 2144 vs 3530 ± 2164 µg · hr/ L). The effect of acute inflammation was not significant (AUC = 4996 ± 3813). Both acute and chronic inflammation also reduced thein vitro plasma protein binding of prednisolone, the reduction being much greater after chronic inflammation. The AUC of free prednisolone after chronic inflammation was 3141 µg · hr/L, compared to 1121 µg · hr/L in the control group and 1823 µg · hr/L after acute inflammation. The mean values of half-life and apparent volume of distribution at steady-state in each group were similar. These results indicate that prednisolone must be used with caution in the treatment of inflammatory diseases because of higher free concentrations of the steroid.     

Age-related changes in brain: II. Positron emission tomography of frontal and temporal lobe glucose metabolism in normal subjects

While many neuropsychological studies have demonstrated age-related performance alterations in tests thought to reflect frontal and temporal lobe function, there is little direct observation and comparison of these hypothesized brain changesin vivo. The cerebral glucose metabolism of frontal, temporal, and cerebellar regions was examined in 40 young ( =27.5±4.9) and 31 elderly ( =67.6 ± 8.8) normal males using PET-FDG. Univariate analysis showed age-related metabolic reductions in all frontal and temporal lobe regions. The reductions ranged from 13%–24% with the greatest changes in the frontal lobes. Multiple regression analyses showed a stronger age relationship with frontal lobe than with temporal lobe metabolism. The dorsal lateral frontal lobe was the region that appears to change most within the frontal lobes. Examination of the temporal lobe showed that age contributed equally to the metabolic variance of both the lateral temporal lobe and hippocampus. These results suggest that age-related metabolic changes exist in both frontal and temporal lobes and that the frontal lobe change is greater.     

Preliminary report of mortality among workers compensated for work-related asthma

BACKGROUND: Although fatalities due to asthma have been reported among subjects with occupational asthma (OA) associated with re-exposure, groups of subjects with work-related asthma have not been systematically followed up for mortality. During a review of compensation claims for asthma in Ontario, we identified 3 respiratory deaths among subjects previously compensated for OA for whom their surviving spouses received death benefits. This suspected "cluster" prompted us to undertake an investigation to examine mortality pattern among workers compensated for work-related asthma. METHODS: Subjects receiving compensation for OA or aggravation of asthma (AA) between 1980 and 1993, and a comparison sample of workers with claims for musculoskeletal injuries during the same period were identified from the Ontario Workers' Compensation Board. We also identified another comparison group of non-compensated asthmatic patients seen at a hospital clinic during the same period. The files of those with work-related asthma were reviewed to determine if OA or AA was adequately documented. Mortality was ascertained by linkage with the Mortality Database at the Ontario Cancer Registry through 1996. We compared the mortality of the three groups with that expected in the general population of Ontario using SMRs, and directly by proportional-hazards regression. RESULTS: The study included 3,070 subjects: 1,112 with work-related OA/AA with adequate documentation, 1,556 with work-related injuries, and 402 patients with non-work-related asthma. Of the 66 deaths identified, only 2 deaths were due to asthma, both in the work-related asthma group: one from the index cluster and one not previously identified. A second index death was coded as dying from COPD not elsewhere classified (ICD9 496), while the third index death also died of asthma but there was not sufficient information documenting OA to include the subject in the analyses. As compared with the general population, there were fewer deaths than expected from most causes, except for deaths among the work-related asthma claimants and the nonwork-related asthma patients from respiratory diseases (SMRs 1.3 and 5.9, respectively; 0.5 among injury claimants), all chronic obstructive lung disease (ICD9 490-496; SMRs 2.3 and 7.7, respectively), and asthma (SMRs 18.2 and 0, respectively). In direct comparison of the work-related asthma claimants with the injury claimants, the risk of death appeared elevated from respiratory disease (RR 2.6) and ischemic heart disease (IHD) (RR 2.8) but the confidence intervals included unity. CONCLUSIONS: This preliminary report raises the possibility that serious outcomes, including excess deaths from respiratory disease, in particular asthma, may occur among those with work-related asthma even in the absence of re-exposure. However, the findings are inconclusive given that the number of deaths was small and we identified only one new asthma death in addition to the index cluster. We also observed for the first time that deaths due to circulatory disease, particularly IHD, may also be increased among such workers; this needs to be confirmed elsewhere.     

A new sesquiterpene lactone from Elephantopus mollis

A methanolic extract of the whole plant of Elephantopus mollis was found to contain lupeol, lupeol acetate, epifriedelinol, molephantin, and 2-de-ethoxy-2-methoxyphantomolin, as well as a new sesquiterpene lactone determined to be 2-de-ethoxy-2-hydroxyphantomolin.     

Reduced cardiotoxicity of doxorubicin given in the form ofN-(2-hydroxypropyl) methacrylamide conjugates: an experimental study in the rat

Summary A rat model was used to evaluate the general acute toxicity and the late cardiotoxicity of 4 mg/kg doxorubicin (DOX) given either as free drug or in the form of threeN-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates. In these HPMA copolymers, DOX was covalently bound via peptide linkages that were either non-biodegradable (Gly-Gly) or degradable by lysosomal proteinases (Gly-Phe-Leu-Gly). In addition, one biodegradable conjugate containing galactosamine was used; this residue was targeted to the liver. Over the first 3 weeks after the i.v. administration of free and polymer-bound DOX, all animals showed a transient reduction in body weight. However, the maximal reduction in body weight seen in animals that received polymer-bound DOX (4 mg/kg) was significantly lower than that observed in those that received free DOX (4 mg/kg) or a mixture of the unmodified parent HPMA copolymer and free DOX (4 mg/kg;P<0.01). Throughout the study (20 weeks), deaths related to cardiotoxicity were observed only in animals that received either free DOX or the mixture of HPMA copolymer and free DOX; in these cases, histological investigations revealed marked changes in the heart that were consistent with DOX-induced cardiotoxicity. Sequential measurements of cardiac output in surviving animals that received either free DOX or the mixture of HPMA copolymer and free DOX showed a reduction of 30% in function beginning at the 4th week after drug administration. The heart rate in these animals was 12% lower than that measured in age-matched control rats (P<0.05). Animals that were given the HPMA copolymer conjugates containing DOX exhibited no significant change in cardiac output throughout the study (P<0.05). In addition, no significant histological change was observed in the hearts of animals that received DOX in the form of HPMA copolymer conjugates and were killed at the end of the study. However, these animals had shown a significant increase in heart rate beginning at 8 weeks after drug administration (P<0.01). This study demonstrates that covalent binding of DOX to HPMA copolymer conjugates via both stable and biodegradable peptidyl linkages considerably reduces both the general acute toxicity and the late cardiotoxicity of DOX in the rat and could offer the potential for improving the therapeutic index in the clinical application of DOX.