Deep wound infection after proximal femoral fracture: consequences and costs.

The purpose of this study was to assess the impact of deep wound infection after surgery for proximal femoral fracture (PFF) on the patient in terms of mortality and social consequences, and on the National Health Service in terms of financial burden. Sixty-one cases of PFF over a six-year period were complicated with deep surgical wound infection. These cases were compared with a matched control group of 122 patients without infection. Infected cases had greatly increased hospital stay (P<0.001), were 4.5 times less likely to survive to discharge (P=0.002), and if they survived, were three times less likely to return to their original residence (P=0.05). The total cost of treatment per infected case was 24,410 pound sterling compared with 7210 pound sterling for controls (P<0.001). Meticillin-resistant Staphylococcus aureus (MRSA) infection increased admission length and cost compared with non-MRSA infection (P=0.02). Deep wound infection after PFF is a devastating and costly complication for both the patient and the healthcare services. The cost consequences should be considered when allocating resources to trauma services to ensure adequate provision to minimize infection risks and to accommodate treatment costs in this vulnerable group.

Androgen-mediated development in male rat offspring exposed to flutamide in utero: permanence and correlation of early postnatal changes in anogenital distance and nipple retention with malformations in androgen-dependent tissues.

Male offspring exposed in utero to antiandrogens often display alterations in androgen-dependent developmental markers (e.g., anogenital distance [AGD], nipple retention) together with clearly adverse responses such as genital malformations and reproductive tract lesions. The objectives of this study were to determine whether in utero exposure to flutamide results in permanent changes in male AGD and nipple retention, characterize the dose-response relationship between flutamide-mediated alterations in these landmarks and clearly adverse antiandrogenic effects, and establish the predictive value and relationship between AGD and nipple retention, and other adverse manifestations. Male offspring were exposed in utero to 0, 6.25, 12.5, 25, or 50 mg/kg/day (po) of flutamide from gestation days 12 to 21. Offspring were uniquely identified at birth, and various androgen-mediated end points (AGD, areola/nipple retention, cryptorchidism, reproductive tract weights, and malformation incidence) were examined throughout life. In utero flutamide exposure significantly decreased the AGD on postnatal day (PND) 1 and increased areola/nipple retention in male rats on PND 13. Flutamide-induced alterations in AGD and areolae/nipples in early postnatal life correlated with a reduction in AGD and retained nipples observed in the adult. Prenatal flutamide exposure resulted in dose-responsive increases in cryptorchidism. Hypospadias were observed in all flutamide-exposed offspring. In utero flutamide exposure induced partial or complete prostate agenesis and decreased the weights of the seminal vesicles, levator ani bulbocavernosus (LABC) muscle, testes, and epididymides in a dose-dependent manner. Epididymal malformations were observed mainly in the 50 mg/kg/day flutamide dose group. In general, flutamide-induced alterations in dihydrotestosterone (DHT)- and testosterone (T)-dependent development each had similar respective dose-response curves. DHT-mediated development was more sensitive to in utero flutamide exposure than T-dependent processes. However, the dose-response curves for flutamide-induced changes in cryptorchidism and seminal vesicle weight were intermediate between the dose-response curves for DHT- and T-mediated development, indicating that proper development of these tissues may require both androgens. The LABC also displayed a dose-dependent decrease in weight that was similar to dose-response observed with seminal vesicle weight and was the most sensitive T-dependent end point measured. Flutamide-induced decreases in AGD predicted subsequent malformations as evidenced by logistic regression and receiver operator characteristic analysis of malformations versus AGD. However, the AGD that would predict a 10% incidence of seminal vesicle malformations is equivalent to a female AGD. An almost fully feminized phenotype of 10-12 nipples was observed in animals that had malformations in T-dependent tissues, whereas 6 or more nipples were observed in animals with malformation in DHT-dependent tissues. These data suggest that flutamide-mediated changes in AGD and nipple retention are not sensitive predictors of altered T-mediated development.

The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat.

Phthalate esters (PE) such as DEHP are high production volume plasticizers used in vinyl floors, food wraps, cosmetics, medical products, and toys. In spite of their widespread and long-term use, most PE have not been adequately tested for transgenerational reproductive toxicity. This is cause for concern, because several recent investigations have shown that DEHP, BBP, DBP, and DINP disrupt reproductive tract development of the male rat in an antiandrogenic manner. The present study explored whether the antiandrogenic action of DEHP occurs by (1) inhibiting testosterone (T) production, or by (2) inhibiting androgen action by binding to the androgen receptor (AR). Maternal DEHP treatment at 750 mg/kg/day from gestational day (GD) 14 to postnatal day (PND) 3 caused a reduction in T production, and reduced testicular and whole-body T levels in fetal and neonatal male rats from GD 17 to PND 2. As a consequence, anogenital distance (AGD) on PND 2 was reduced by 36% in exposed male, but not female, offspring. By GD 20, DEHP treatment also reduced testis weight. Histopathological evaluations revealed that testes in the DEHP treatment group displayed enhanced 3ss-HSD staining and increased numbers of multifocal areas of Leydig cell hyperplasia as well as multinucleated gonocytes as compared to controls at GD 20 and PND 3. In contrast to the effects of DEHP on T levels in vivo, neither DEHP nor its metabolite MEHP displayed affinity for the human androgen receptor at concentrations up to 10 microM in vitro. These data indicate that DEHP disrupts male rat sexual differentiation by reducing T to female levels in the fetal male rat during a critical stage of reproductive tract differentiation.

Effects of in utero exposure to linuron on androgen-dependent reproductive development in the male Crl:CD(SD)BR rat.

Linuron (3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea) is a herbicide that blocks androgen action in the male rat. Studies were undertaken to characterize the ability of linuron to activate transcription through the human androgen receptor (AR) in vitro and to determine whether in utero linuron exposure induces dose-responsive alterations in androgen-dependent reproductive development in the male rat. In vitro, linuron competitively antagonized transcriptional activity of the AR induced by dihydrotestosterone (DHT) in a dose-responsive manner with an equilibrium dissociation constant (K(B)) of 75.8 x 10(-8) M. Pregnant rats were administered linuron by gavage at 0, 12.5, 25, or 50 mg/kg/day (n = 11/group) from gestation day 12 to 21. Anogenital distance of resulting offspring was unaffected, whereas male areola/nipple retention was increased in a dose-responsive manner. Hypoplastic testes in adult offspring were seen in 2/56 rats (2/10 litters), 8/69 rats (4/11 litters), and 5/44 rats (3/8 litters), while hypoplastic epididymides occurred in 1/56 rats (1/10 litters), 8/69 rats (4/11 litters), and 2/44 rats (1/8 litters) in the 12.5, 25, and 50 mg/kg/day dose groups, respectively. Partial agenesis of the epididymides was observed in 3/44 rats (2/8 litters) only in the 50 mg/kg/day group. These data indicate that in utero exposure to linuron preferentially impairs testosterone-mediated, rather than DHT-mediated, reproductive development. This effect is distinctly different from the effects induced by flutamide, an AR antagonist that shares structural similarities with linuron. Furthermore, these data suggest that dose-response studies utilizing late gestational exposure to endocrine-active compounds may be more robust than the traditional or EPA-modified multigeneration protocols in identifying adverse effects.