Imprinted genes tend to occur in clusters. We have identified a cluster in distal mouse chromosome (Chr) 2, known from early genetic studies to contain both maternally and paternally imprinted, but unspecified, genes. Subsequently, one was identified as Gnas, which encodes a G protein ␣ subunit, and there is clinical and biochemical evidence that the human homologue GNAS1, mutated in patients with Albright hereditary osteodystrophy, is also imprinted. We have used representational difference analysis, based on parent-of-origin methylation differences, to isolate candidate imprinted genes in distal Chr 2 and found two oppositely imprinted genes, Gnasxl and Nesp. Gnasxl determines a variant G protein ␣ subunit associated with the trans-Golgi network and Nesp encodes a secreted protein of neuroendocrine tissues. Gnasxl is maternally methylated in genomic DNA and encodes a paternal-specific transcript, whereas Nesp is paternally methylated with maternal-specific expression. Their reciprocal imprinting may offer insight into the distal Chr 2 imprinting phenotypes. Remarkably, Gnasxl, Nesp, and Gnas are all part of the same transcription unit; transcripts for Gnasxl and Nesp are alternatively spliced onto exon 2 of Gnas. This demonstrates an imprinting mechanism in which two oppositely imprinted genes share the same downstream exons.

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This randomized, active-controlled study evaluated the extent and duration of analgesia after administration of liposome bupivacaine (LB), a novel formulation of bupivacaine, compared with bupivacaine HCl given via local infiltration in excisional hemorrhoidectomy. One hundred patients were randomly assigned to receive a single dose of bupivacaine HCl 75 mg (0.25% with 1:200,000 epinephrine) or LB 66, 199, or 266 mg upon completion of hemorrhoidectomy. Postoperative pain intensity was assessed using a numeric rating scale at rest to calculate a cumulative pain score (area under the curve). Cumulative pain scores were significantly lower with LB at each study dose ( P < 0.05) compared with bupivacaine HCl 72 hours after surgery. Post hoc analysis showed that mean total postoperative opioid consumption was statistically significantly lower for the LB 266-mg group compared with the bupivacaine HCl group during the 12- to 72-hour postoperative period ( P = 0.019). Median time to first opioid use was 19 hours for LB 266 mg versus 8 hours for bupivacaine HCl ( P = 0.005). Incidence of opioid-related adverse events was 4 per cent for LB 266 mg compared with 35 per cent for bupivacaine HCl ( P = 0.007). Local infiltration with LB resulted in significantly reduced postsurgical pain compared with bupivacaine HCl in patients after hemorrhoidectomy surgery.

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PCB residues are found in biota all over the world. A biologic magnification of PCBs has been demonstrated in the food chain: plankton-fish-fish eating birds. A world map of the PCBs residues in biota and some of their biologic effects are given in this study. The biologic effects of PCBs are varied and may generally be explained by the induction or inhibition of the activity of a large number of enzymes, which upsets quantitatively, normal biochemical processes. Harm to reproduction, growth, development, defense systems, tissues, and organs appeared in susceptible organisms as a result of such changes or as a chain reaction to heterostases. The adverse health effects, observed in persons occupationally exposed and in those accidentally poisoned, point to the risk for the general population of an ever-increasing environmental pollution by PCBs. There is need for an integrated approach, consisting of epidemiologic studies on high risk groups in the general population and in persons occupationally exposed, as well as periodic assessment of PCB residues in man, his food, and feed supplies.

No difference in perceived pain was found between the groups. The results of this small, unstratified study indicate that continuous infusion of bupivacaine at iliac crest bone-graft sites during the postoperative period is not an effective pain-control measure in hospitalized patients receiving systemic narcotic medication.

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