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     

Sentinel lymph node biopsy in breast cancer: unfiltered radioisotope is superior to filtered

BACKGROUND: The combination of gamma-probe radiolocalization and blue-dye mapping of sentinel lymph nodes (SLNs) has been advocated as the most accurate method for staging the clinically negative axilla in breast cancer patients, but the technical aspects of these procedures are not fully characterized in the literature. In this study, we compared the success of SLN localization in 134 consecutive breast cancer patients using blue dye plus two different preparations of radiocolloid. STUDY DESIGN: A retrospective analysis of a prospectively maintained data base was performed to assess SLN localization in two cohorts of patients. Unfiltered technetium-99m (Tc-99m) sulfur colloid (in 77 patients; group I) was compared with filtered Tc-99m sulfur colloid (in 57 patients; group II). All patients had a peritumoral injection of blue dye and isotope, followed immediately by lymphoscintigraphy to confirm radioactivity at the injection site and to image the SLN. Statistical analysis was performed using the Pearson chi-square test. RESULTS: Unfiltered Tc-99m sulfur colloid was superior to the filtered radiocolloid in localizing the SLN (88% versus 73%; p = 0.03). SLN imaging by lymphoscintigraphy was also more successful in the unfiltered group. Using the combination of blue dye and radiolocalization, SLNs were identified in 94% of patients. CONCLUSIONS: For optimal localization of the SLN in breast cancer patients, surgeons should use the combined technique of blue-dye mapping and gamma-probe localization using unfiltered Tc-99m sulfur colloid.     

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.     

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.     

The protective activity of ICRF-187 against doxorubicin-induced cardiotoxicity in the rat

Summary The protective activity of the bisdioxopiperazine ICRF-187 against the cardiotoxicity of doxorubicin was evaluated in the rat using both functional and histological assays. Animals that had received a single i. v. dose of doxorubicin (4 mg/kg) alone were compared with those that had been pretreated with a single i. v. injection of saline or ICRF-187 (40 or 60 mg/kg). All rats showed a transient reduction in body weight during the first 3 weeks after drug administration. The greatest reduction (16%) was observed in animals that had received a combination of ICRF-187 (40 or 60 mg/kg) and doxorubicin. Deaths related to cardiotoxicity were observed only in rats that had received doxorubicin alone and in those treated with saline; most of the deaths occurred at between 8 and 13 weeks after drug administration. Sequential assessments of heart function showed a persistent depression of cardiac output in animals that had received doxorubicin, with or without pretreatment with ICRF-187. The reduction in cardiac output observed in rats that had been pretreated with ICRF-187 (40 or 60 mg/kg) amounted to 15% and 30% after 12 and 20 weeks, respectively, indicating that cardioprotection was only partial. Nevertheless, this represented a marked improvement as compared with the 35% reduction in cardiac output measured at 12 weeks in animals that had received doxorubicin but without pretreatment with ICRF-187. Histological examination of animals that had died during the course of the study and had received doxorubicin after pretreatment with saline revealed severe myocardial lesions typical of doxorubicin-induced damage. In contrast, animals that had been pretreated with ICRF-187 and survived for up to 20 weeks after treatment showed a marked amelioration of these lesions. The present findings may be interpreted as a true cardioprotection or a delay in the onset of the cardiotoxicity of doxorubicin resulting from pretreatment with the bisdioxopiperazine ICRF-187. Although prior and ongoing clinical trials clearly indicate that ICRF-187 protects patients well against doxorubicin-induced heart damage, further investigations are required beforehigh doses of ICRF-187 can be used as a means of increasing the protective activity of this drug against doxorubicin-induced cardiotoxicity.This work was supported by the Cancer Research Campaign     

In vivo CT measurement of blood-brain transfer constant of iopamidol in human brain tumors

Summary We have developed an in vivo method of measuring the blood-brain transfer constant (K) of iopamidol and the cerebral plasma volume (V_p) in brain tumors using a clinical X-ray CT scanner. In patient studies, Isovue 300 (iopamidol) was injected at a dosage of 1 ml/kg patient body weight. Serial CT scans of the tumor site and arterial blood samples from a radial artery were taken up to 48 min after injection. The leakage of iopamidol into the brain through the blood-brain barrier was modelled as an exchange process between two compartments, the intravascular plasma space and the tissue interstitial space. Using this model and the concentration measurements in blood plasma and tissue, quantitative estimates of K and V_p in brain tumors were obtained. In addition, distribution of the estimated values of K and V_p in tumors were displayed as false colour functional images overlaid on the conventional CT scan.In a study of twelve patients with anaplastic astrocytoma (n = 3), glioblastoma multiforme (n = 4) or metastases (n = 5) the mean K and VP values in tumor were found to be 0.0273 ± 0.0060 ml/min/g and 0.068 ± 0.11 ml/g respectively. These values were significantly higher than those in grey or white matter in the contralateral normal hemisphere (p < 0.05). The functional images showed variations in K and V_p within the tumor which were difficult to perceive in the original contrast enhanced CT scans.     

Maturation of epididymal spermatozoa in the nondomesticated guinea pigs Cavia aperea and Galea musteloides

The physiological changes occurring in spermatozoa in the male reproductive tract of 2 nondomesticated species of South American guinea pigs with different mating systems were studied. Cavia aperea, the wild ancestor of the domesticated guinea pig, has a polygynous mating system, whereas Galea musteloides exhibits promiscuous mating behavior. The epididymis of both species resembled that of the domesticated guinea pig, with a swathe of tubule convolutions (linking the 2 major parts of the organ) that was of smaller size in Cavia but not Galea. Higher relative epididymal weight was demonstrated in the promiscuous species. During their journey through the epididymis, spermatozoa from Galea developed their potential for motility expression more proximally than did those of Cavia, but motility developed into forward progression in the same region in both species. The maximal velocities exhibited by mature Cavia sperm in vitro were greater than those of Galea. Spermatozoa from Cavia were twice the length of those from Galea, they had larger heads, and the acrosomes of single sperm were more sensitive to disruption during morphological preparation. Only in Cavia did agglutination of sperm into rouleaux occur, after the potential for motility had been developed. Migration of the cytoplasmic droplet along the midpiece occurred in the same regions in both species and before agglutination in Cavia. It is suggested that the male's reproductive strategy (polygyny vs promiscuity) dictates the size of the testis and epididymis, whereas the female's reproductive physiology (induced ovulation vs cyclicity) influences the posttesticular development of sperm morphology and motility in the epididymis.     

Dietary conjugated linoleic acid mixture affects the activity of intestinal acyl coenzyme A: cholesterol acyltransferase in hamsters

The present study was designed to study the mechanisms by which dietary conjugated linoleic acids (CLA) decrease serum cholesterol. Hamsters were fed a semi-synthetic diet containing 1 g cholesterol/kg diet with or without supplementation with 20 g linoleic acid (LA) and 20 g CLA/kg diet. After 8 weeks, serum fasting total cholesterol (TC) and triacylglycerol (TG) were significantly lower in the LA-supplemented and CLA-supplemented groups compared with those of the control (CTL) hamsters. In contrast to LA, CLA significantly lowered hepatic cholesterol but it increased the level of adipose tissue cholesterol, suggesting that the hypocholesterolaemic mechanism of CLA is different from that of LA. CLA decreased the activity of intestinal acyl CoA:cholesterol acyltransferase (ACAT) whereas LA had no effect on this enzyme. Consequently, CLA supplementation increased the faecal excretion of total neutral sterols, but it had no or little effect on the faecal acidic sterols. If the ACAT is associated with cholesterol absorption, the part of mechanisms by which CLA decreases serum cholesterol may involve down-regulation of intestinal ACAT activity.