Reciprocal relationships between general (Propofol) anesthesia and circadian time in rats.

Several common postdischarge symptoms, such as sleep disorders, headache, drowsiness or general malaise, evoke disturbances of circadian rhythms due to jet lag (ie crossing time zones) or shift work rotation. Considering that general anesthesia is associated with numerous effects on the central nervous system, we hypothesized that it may also act on the circadian timing system. We first determined the effects of the circadian timing on general anesthesia. We observed that identical doses of propofol showed marked circadian fluctuations in duration of effects, with a peak at the middle of the resting period (ie 7 h after lights on). Then, we examined the effects of general anesthesia on circadian timing, by analysing stable free-running circadian rhythms (ie in constant environmental conditions), an experimental approach used widely in circadian biology. Free-running rats were housed in constant darkness and temperature to assess possible phase-shifting effects of propofol anesthesia according to the time of the day. When administered around (+/-2 h) the daily rest/activity transition point, a 30-min propofol anesthesia induced a 1-h phase advance in the free-running rest-activity rhythm, while anesthesia had no significant resetting effect at other times of the day. Anesthesia-induced hypothermia was not correlated with the phase-shifting effects of propofol anesthesia. From our results, anesthesia itself can reset circadian timing, and acts as a synchronizing cue for the circadian clock.     

Recognition and management of patients with high-risk vesicovaginal fistulas: Implications for teaching and research

Vesicovaginal fistulas (VVFs) occurring as a result of obstetric trauma are a vast problem in Nigeria and Ghana, where at least 20 000 women await repair, and fewer than 50 physicians have the necessary expertise. Through a series of conferences those VVFs that are at high risk and those at low-risk for repair failure, were identified. A clinic was established where repair of low-risk VVFs was done on an ongoing basis in a remote region of Ghana. A visiting surgical team was utilized to repair the difficult, or high-risk, VVFs, which included 4–6 cm VVFs (3), recurrent VVF (1), combined VVF and RVF (rectovaginal fistula), a large 5 cm juxtacervical VVF (1), and a vesicouterine fistula (1). Management of these patients and others with VVF repair complications is discussed.     

Influence of statins on postoperative wound complications after inguinal or ventral herniorrhaphy

The lipid-lowering agents, statins, are the most commonly prescribed class of drugs in the western world. Because of their widespread use, many patients undergo surgical procedures while on statins. Statins, in addition to cholesterol-lowering effects, also have anticoagulant, immunosuppressive, and antiproliferative properties that may affect the risk of local wound complications. This study investigated the relationship between statins and postoperative wound complications in a large cohort of patients undergoing inguinal or ventral hernia repair. Data mining was performed in the Veterans Integrated Service Network (VISN)16 Data Warehouse. This database contains clinical and demographic information about all veterans cared for at the ten VA Medical Centers that comprise the South Central VA Healthcare Network in the mid-south region of the US. Aggregate data (age, body mass index, smoking history, gender, race, history of diabetes, statin use, and postoperative wound complications) were obtained for all patients who underwent inguinal or ventral hernia repair during the period October 1, 1996–November 30, 2004. During the period of the query, 10,782 patients (10,676 male, 106 female), 1,242 (11.5%) of whom received statins, underwent herniorrhaphy. Statin use did not affect the risk of wound infection or delayed wound healing. Statin use was, however, associated with an increased rate of local postoperative bleeding complications (P=0.01). When the type of hernia, age, smoking, diabetes, and body mass index were included in a multivariate analysis, statins remained borderline significant as an independent predictor of wound hematoma/postoperative bleeding (P=0.04), odds ratio 1.6 (95% CI 1.03–2.44). Patients who undergo inguinal herniorrhaphy while on statins have an increased risk of postoperative wound hematoma/hemorrhage. Focus on additional factors that may affect the propensity to postoperative bleeding and on meticulous intraoperative hemostasis are particularly important in such patients.     

Role of the EGF-like domains in mammalian tolloid (mTLD) secretion and procollagen C-proteinase activity

Introduction Bone morphogenetic protein (BMP)‐1 and its larger splice variant mammalian tolloid (mTLD) belong to the tolloid group of astacin‐like metalloproteinases that are fundamental to tissue patterning and extracellular matrix assembly. BMP‐1 and mTLD exhibit similar substrate specificity in vitro; however, BMP‐1 is a much better procollagen C‐proteinase than mTLD. mTLD consists of a prodomain (which is cleaved by a furin‐like enzyme) ( Leighton & Kadler 2003 ), a zinc metalloproteinase domain and a C‐terminal part comprising five CUB domains thought to be important for protein–protein interactions ( Hartigan et al. 2003 ), and two EGF‐like domains, which in other proteins are involved in calcium ion binding. BMP‐1 lacks the most C‐terminal two CUB domains and one EGF‐like domain. mTLD activity is known to be calcium ion dependent, as demonstrated for the chick homologue ( Hojima et al. 1985 ). In our current work, we are studying the role of the EGF‐like domains in the secretion and procollagen C‐proteinase activity of mTLD, and the contribution that these domains made to calcium ion dependency. Materials and methods We designed proteins lacking EGF1, EGF2 or both. NotI sites were introduced by PCR at the borders of the EGF domain of a cDNA clone encoding a V5‐His mTLD. Restriction enzyme digestion was used to delete individual domains. The mutant constructs in pCEP4 were stably transfected into 293‐EBNA cells. Expression was analysed by Western blot. The wild‐type and the mutant enzymes were purified on a nickel ion column, and their activity was determined by cleavage of type‐I procollagen in the presence or absence of 5 mm CaCl₂. Results We showed that (1) the mTLD proteins lacking EGF1, EGF2 or EGF1 + EGF2 were poorly secreted into the culture medium compared to mTLD and (2) the EGF deletion mutants remained calcium ion dependent, but some differences were seen. Most notably, the ΔEGF2 and ΔEGF1 + ΔEGF2 mutants were found to be better C‐proteinases than the wild‐type enzyme in the presence of calcium ions. Conclusion From these preliminary data, we concluded that (1) the EGF domains are necessary for efficient secretion (2) both EGF1 and EGF2 domains contribute to the calcium ion dependency of mTLD and (3) the EGF2 domain might be a Ca²⁺‐activated hinge that ‘swings’ the CUB‐4 and CUB‐5 domains away from the active site. The ?EGF2 mTLD might be expected to have an open conformation, thereby making it a better C‐proteinase than the wild‐type enzyme, and (?4) Ca²⁺ ions are bound by other domains in mTLD and not only by the EGF‐like domains.     

Use of health care services for psychological distress by immigrants in an urban multicultural milieu.

OBJECTIVE: Research in the United States tends to attribute low rates of use of mental health services by immigrants to economic barriers. The purpose of our study was to examine this issue in the context of Canada's universal health care system. METHODS: A survey of the catchment area of a comprehensive clinic in Montreal interviewed random samples of 924 Canadian-born individuals and 776 immigrants born in the Caribbean (n = 264), Vietnam (n = 234), or the Philippines (n = 278) to assess their health care use for somatic symptoms, psychological distress, and recent life events. RESULTS: Overall rates of use of medical services in the past year were similar in immigrant (78.5%) and nonimmigrant (76.5%) groups. Rates of use of health care services for psychological distress were significantly lower among immigrants (5.5% compared with 14.7%, P < 0.001). This difference was attributable both to a lower rate of use of specialty mental health services by immigrants (2.5% compared with 11.7%, P < 0.001) and to differential use of medical services for psychological distress (3.5% compared with 5.8%, P = 0.02). When level of psychological distress was controlled, Vietnamese and Filipino immigrants were one-third as likely as Canadian-born residents to make use of mental health services. The lower rate of use by immigrants could not be explained by differences in sociodemographics, somatic or psychological symptoms, length of stay in Canada, or use of alternative sources of help. CONCLUSION: Immigrant status is associated with lower rates of use of mental health services, even with universal health insurance. This lower rate of use likely reflects cultural and linguistic barriers to care.