Spontaneous abortion following mid-trimester amniocentesis. Clinical significance of placental perforation and blood-stained amniotic fluid

The clinical significance of placental perforation and blood-stained amniotic fluid was studied in a group of 7238 Danish women undergoing mid-trimester amniocentesis for prenatal diagnosis under ultrasound guidance. The risk of spontaneous abortion was significantly increased both in pregnancies where the placenta was perforated and in those with blood-stained amniotic fluid. The risk estimate nearly doubled after placental perforation and more than doubled with a bloody tap. It is concluded that for women at relatively low risk of a fetal genetic abnormality, the indication of the amniocentesis should be reconsidered if a placental perforation is unavoidable.     

Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment

The tumor microenvironment consists of tumor, immune, stromal, and inflammatory cells which produce cytokines, growth factors, and adhesion molecules that promote tumor progression and metastasis. Of particular interest in this setting is interleukin-1 (IL-1), a pleiotropic cytokine with numerous roles in both physiological and pathological states. It is known to be up regulated in many tumor types and has been implicated as a factor in tumor progression via the expression of metastatic and angiogenic genes and growth factors. A number of studies have reported that high IL-1 concentrations within the tumor microenvironment are associated with a more virulent tumor phenotype. Solid tumors in which IL-1 has been shown to be up regulated include breast, colon, lung, head and neck cancers, and melanomas, and patients with IL-1 producing tumors have generally bad prognoses. The exact mechanisms by which IL-1 promotes tumor growth remain unclear, though the protein is believed to act via induction of pro-metastatic genes such as matrix metalloproteinases and through the stimulation of adjacent cells to produce angiogenic proteins and growth factors such as VEGF, IL-8, IL-6, TNFα, and TGFβ. The IL-1 receptor antagonist (IL-1ra) is a naturally occurring inhibitor to IL-1 and acts by binding to the IL-1 receptor without activating it. The protein has been shown to decrease tumor growth, angiogenesis, and metastases in murine xenograft models. Our focus in this review is to summarize the known data on the role of IL-1 in tumor progression and metastasis and the use of IL-1 inhibition as a novel therapeutic approach in the treatment of solid organ malignancies.     

Brain protection at the blood-cerebrospinal fluid interface involves a glutathione-dependent metabolic barrier mechanism.

The choroid plexuses (CPs) form a protective interface between the blood and the ventricular cerebrospinal fluid (CSF). To probe into the pathways by which CPs provide brain protection, we sought to evaluate the efficiency of glutathione conjugation in this barrier as a mechanism to prevent the entry of blood-borne electrophilic, potentially toxic compounds into the CSF, and we investigated the fate of the resulting metabolites. Rat CPs, as well as human CPs from both fetal and adult brains, displayed high glutathione-S-transferase activities. Using an in vitro model of the blood-CSF barrier consisting of choroidal epithelial cells cultured in a two-chambered device, we showed that glutathione conjugation can efficiently prevent the entry of 1-chloro-2,4-dinitrobenzene (CDNB) into the CSF, a model for electrophilic compounds. The duration of this enzymatic protection was set by the concentration of CDNB to which the epithelium was exposed, and this barrier effect was impaired only on severe epithelial intracellular glutathione and cysteine depletion. The conjugate was excreted from the choroidal cells in a polarized manner, mostly at the blood-facing membrane, via a high-capacity transport process, which is not a rate-limiting step in this detoxification pathway, and which may involve transporters of the ATP-binding cassette c(Abcc) and/or solute carrier 21 (Slc21) families. Supplying the choroidal epithelium at the blood-facing membrane with a therapeutically relevant concentration of N-acetylcysteine sustained this neuroprotective effect. Thus, glutathione conjugation at the CP epithelium coupled with the basolateral efflux of the resulting metabolites form an efficient blood-CSF enzymatic barrier, which can be enhanced by pharmacologically increasing glutathione synthesis within the epithelial cells.     

How often do asymptomatic healthcare workers cause methicillin-resistant Staphylococcus aureus outbreaks? A systematic evaluation.

A systematic search was performed to identify outbreaks of methicillin-resistant Staphylococcus aureus infection and colonization caused by healthcare workers (HCWs). Of 191 outbreaks identified, 11 had strong epidemiological evidence that HCWs were the source. In 3 of these outbreaks, asymptomatic carriers were the cause. The frequent practice of screening asymptomatic HCWs should be reconsidered.     

Penetrating intracranial wood wounds: clinical limitations of computerized tomography

The case history of a patient with a periorbital penetrating wooden foreign body is presented. The computerized tomography (CT) densities of several different sources of wood were compared using an experimental model. The clinical usefulness and practical limitations of CT in the evaluation of intracranial foreign bodies is discussed, and the management of this type of injury is reviewed.     

Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and during mobilization after major abdominal surgery.

In a double-blind, randomized study, epidural infusions of low-dose morphine (0.2 mg/h) combined with low-dose bupivacaine (10 mg/h) were compared with epidural infusions of low-dose morphine (0.2 mg/h) alone for postoperative analgesia at rest and during mobilization and cough in 24 patients after elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during mobilization from the supine into the sitting position 12 and 30 h after surgical incision and during cough 8, 12, and 30 h after surgical incision (P less than 0.05). We conclude, that low-dose epidural bupivacaine potentiates postoperative low-dose epidural morphine analgesia during mobilization and cough. Evaluation of postoperative analgesic regimens should include assessment of pain during various activities as different analgesics may have differential effects on pain at rest and during mobilization.