Impact Melt Facies in the Moon's Crisium Basin: Identifying, Characterizing, and Future Radiogenic Dating.

Both Earth and the Moon share a common history regarding the epoch of large basin formation, though only the lunar geologic record preserves any appreciable record of this Late Heavy Bombardment. The emergence of Earth's first life is approximately contemporaneous with the Late Heavy Bombardment; understanding the latter informs the environmental conditions of the former, which are likely necessary to constrain the mechanisms of abiogenesis. While the relative formation time of most of the Moon's large basins is known, the absolute timing is not. The timing of Crisium Basin's formation is one of many important events that must be constrained and would require identifying and dating impact melt formed in the Crisium event. To inform a future lunar sample dating mission, we thus characterized possible outcrops of impact melt. We determined that several mare lava-embayed kipukas could contain impact melt, though the rim and central peaks of the partially lava-flooded Yerkes Crater likely contain the most pure and intact Crisium impact melt. It is here where future robotic and/or human missions could confidently add a key missing piece to the puzzle of the combined issues of early Earth-Moon bombardment and the emergence of life.

Effect of anaesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro.

BACKGROUND: Metastatic recurrence is the main cause of breast cancer-related deaths. Tumour cell proliferation and migration are crucial steps in the metastatic process. Several perioperative factors, including general anaesthesia and opioid analgesia, adversely affect immune function, potentially increasing metastatic recurrence. Regional anaesthesia-analgesia has been consistently shown to attenuate the stress response to surgery, and also reduce opioid and general anaesthesia requirements, thereby attenuating this perioperative immunosuppression. We investigated the effect of serum from breast cancer surgery patients who received different anaesthetic techniques on breast cancer cell function in vitro. METHODS: Patients were randomized to receive propofol/paravertebral anaesthesia-analgesia (propofol/paravertebral, n=11) or sevoflurane general anaesthesia with opioid analgesia (sevoflurane/opioid, n=11). The ER-negative MDA-MB-231 cell line was treated with patient serum from both groups. The effects on proliferation and migration were measured. RESULTS: Treatment groups were well balanced for age, weight, surgical procedure, and cancer pathology. Pain scores were lower at 1 and 2 h in the propofol/paravertebral analgesia group. Compared with preoperative values, proliferation of MDA-MB-231 cells treated with postoperative patient serum at 10% concentration from the propofol/paravertebral group was significantly reduced compared with the sevoflurane/opioid group (-24% vs 73%, P=0.01). There was no significant change in MDA-MB-231 cell migration after treatment with patient serum between the two groups. CONCLUSIONS: Serum from patients receiving propofol/paravertebral anaesthesia for breast cancer surgery inhibited proliferation, but not migration, of ER-MDA-MB-231 cells in vitro, to a greater extent than that from patients receiving sevoflurane/opioid anaesthesia-analgesia. This implies that anaesthetic technique alters the serum molecular milieu in ways that may affect breast cancer cell function, possibly by altering anaesthetic and opioid drug administration and resultant pain scores.

Fentanyl and clonidine as adjunctive analgesics with levobupivacaine in paravertebral analgesia for breast surgery.

The addition of fentanyl or clonidine to levobupivacaine was evaluated in patients undergoing breast surgery under general anaesthesia with intra- and postoperative paravertebral analgesia. Patients were randomly allocated to four groups: Group L received 19 ml bolus levobupivacaine 0.25% plus 1 ml saline followed by an infusion of levobupivacaine 0.1%; Group LF received 19 ml bolus levobupivacaine 0.25% plus fentanyl 50 microg followed by an infusion of levobupivacaine 0.05% with fentanyl 4 microg x ml(-1); Group LC received 19 ml bolus levobupivacaine 0.25% plus clonidine 150 microg followed by an infusion of levobupivacaine 0.05% with clonidine 3 microg x ml(-1); Group C (control) received general anaesthesia without paravertebral analgesia. All groups received postoperative i.v. morphine patient controlled analgesia (PCA). Although mean (SD) postoperative PCA morphine consumption was decreased in LF [7.9 (4.1) mg] and LC [5.9 (3.5) mg]vs L [27.7 (8.6) mg] or C patients [21.7 (5.5) mg], p < 0.01, paravertebral fentanyl and clonidine were associated with significantly increased vomiting and hypotension, respectively.

Inhibition of the stress response to breast cancer surgery by regional anesthesia and analgesia does not affect vascular endothelial growth factor and prostaglandin E2.

Angiogenesis is essential for breast cancer metastases formation and is mediated by vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2). We hypothesized that serum levels of VEGF and PGE2 are increased by the stress response to breast cancer surgery and attenuated by paravertebral anesthesia and analgesia (PVAA). Thirty women undergoing mastectomy were enrolled in this prospective, randomized study, to receive general anesthesia (GA) and postoperative opioid analgesia (morphine 0.1 mg/kg bolus and patient-controlled infusion) or GA and PVAA (72-h infusion). All patients received rectal diclofenac. Venous blood samples were taken preoperatively and at 4 and 24 h postoperatively for serum glucose, cortisol, C-reactive protein, VEGF, and PGE2. PVAA inhibited the surgical stress response, as indicated by significantly less plasma glucose, cortisol, and C-reactive protein. VEGF and PGE2 values did not differ significantly between the groups. Mean (SD) percentage change in VEGF at 4 and 24 h respectively were 3% +/- 44% versus 9% +/- 80%, P=0.29 and 5% +/- 43% versus -10% +/- 63%, P=0.41 for patients with combined general and PVAA and GA alone, respectively. Mean percentage change in postoperative PGE2 at 4 and 24 h respectively was 10% +/- 17% versus 11% +/- 69%, P=0.29 and 34% +/- 19% versus 47% +/- 18%, P=0.15. We conclude that despite inhibiting the surgical stress response, PVAA had no effect on serum levels of putative breast cancer angiogenic factors, VEGF and PGE2.

Intraperitoneal pethidine versus intramuscular pethidine for the relief of pain after laparoscopic cholecystectomy: randomized trial.

Laparoscopic cholecystectomy is widely used and may be performed as an ambulatory procedure. We undertook a randomized comparison of the benefits of intraperitoneal pethidine compared with intramuscular pethidine for postoperative analgesia following laparoscopic cholecystectomy. A series of 100 consecutive American Society of Anesthesiologists (ASA) I or II patients were randomly assigned to intramuscular pethidine (54 patients) or intraperitoneal pethidine (46 patients). Each was combined with intraperitoneal bupivacaine. The primary endpoints were the pain and nausea scores at intervals after operation. All recruited patients completed the study. Pain scores at rest and upon movement were significantly lower in the group receiving the intraperitoneal pethidine at each of the time periods examined (pain at rest at 4 hours: 1.6 +/- 0.8 vs. 2.4 +/- 0.9 cm; p < 0.001; pain upon movement at 4 hours: 2.1 +/- 0.9 vs. 3.1 +/- 1.2 cm; p < 0.001). The total dose of pethidine administered via patient-controlled analgesia (PCA) during the first 24 hours after surgery was also significantly lower in this group (total dose 50.9 +/- 3.9 vs. 55.9 +/- 4.4 mg; p < 0.001). There were no significant differences in the respiratory rate at any of the time periods. Intraperitoneal pethidine analgesia was superior to an equivalent dose of intramuscular pethidine for the relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. This was achieved at the expense of increased nausea but no significant increase in vomiting. The accessibility of this route of analgesia administration has implications for patients undergoing laparoscopic procedures, particularly with the recent trend toward increased use of ambulatory techniques.

Tissue cytokine and chemokine expression in inflammatory bowel disease.

OBJECTIVE AND DESIGN: This study aimed to determine if mucosal expression of the chemokines IL-8, RANTES and MCP-1 and the pro-inflammatory cytokines TNFalpha and IL-6 are elevated in patients with inflammatory bowel disease. MATERIALS AND SUBJECTS: Intestinal mucosa samples were obtained at the time of surgical resection, n = 16 from each of the following groups: normal/control, CD and UC. METHODS: An homogenate was prepared of each tissue sample and cytokines measured by ELISA. RESULTS: IL-8 was significantly increased in both disease groups compared to controls Similarly, RANTES levels were also significantly increased. MCP-1 levels were increased in both disease groups, this increase was statistically significant in the UC group only. TNFalpha and IL-6 were significantly increased in the CD group only. CONCLUSIONS: Chemokines, together with key cytokines that promote their release are elevated in mucosal tissues from patients with IBD. It is likely that these chemokines play an important role in the perpetuation of tissue destructive inflammatory processes.

Pulmonary embolism following tonsillectomy.

Acute post-operative pulmonary embolism is a serious potentially life-threatening complication which is not anticipated in young patients undergoing non-major surgery. We report a case in which a 32-year-old previously healthy woman developed a major pulmonary embolism following tonsillectomy. Subsequent investigations revealed the presence of an occult malignancy. This case highlights the role of paraneoplastic hypercoagulable states in the aetiology of venous thromboembolism and the importance of thromboprophylaxis in the presence of confirmed or suspected malignancy. To our knowledge no case of major pulmonary embolism occurring after tonsillectomy has been previously reported.

Human colonic anti-secretory activity of the potent NK(1) antagonist, SR140333: assessment of potential anti-diarrhoeal activity in food allergy and inflammatory bowel disease.

1. This in vitro study was designed to determine the potential use of the NK(1) antagonist, SR140333 as an anti-diarrhoeal treatment for food allergy or inflammatory bowel disease. The effect of various immune and neuronal stimuli on human colonic substance P (SP) release and the effect of SR140333 on subsequently stimulated mucosal ion transport was investigated. 2. Submucosal and sensory nerve fibre stimulation using electrical field stimulation (1 ms/7 Hz/7 V) and capsaicin (50 microM) respectively, mast cell activation by anti-IgE (1/250 dilution) and granulocyte stimulation using fMLP (50 microM) each released SP and evoked a secretory response. 3. SP and the NK(1) selective agonist, Sar-SP (0.1 - 1000 nM) stimulated an increase in colonic secretion which was antagonized by SR140333 (pD'(2)=6.7 and 7.25 versus SP and Sar-SP respectively). 4. SR140333, at a concentration that blocked NK(1)-mediated secretion (500 nM), also reduced the secretory response to both alphaIgE and capsaicin. This suggests a pathophysiologic role for NK(1) receptors. 5. Capsaicin evoked SP release was increased in tissue taken from Crohn's disease but not ulcerative colitis patients. The response to SP was however reduced by 70 and 89% respectively. 6. Mast cells and sensory afferents contribute to allergic diarrhoea. Since SR140333 reduced the secretory response to mast cell and afferent stimulation this compound may be particularly useful in reducing the symptoms of food allergy.

Self-reported body mass index and health-related quality of life: findings from the Behavioral Risk Factor Surveillance System.

OBJECTIVE: To examine the relationship between self-reported body mass index (BMI) and health-related quality of life in the general adult population in the United STATES: RESEARCH METHODS AND PROCEDURES: Using data from 109,076 respondents in the 1996 Behavioral Risk Factor Surveillance System, we examined how self-reported BMI is associated with five health-related quality of life measures developed by the Centers for Disease Control and Prevention for population health surveillance. RESULTS: After adjusting for age, gender, race or ethnicity, educational attainment, employment status, smoking status, and physical activity status, participants with a self-reported BMI of <18.5 kg/m(2) and participants with a self-reported BMI of > or =30 kg/m(2) reported impaired quality of life. Compared with persons with a self-reported BMI of 18.5 to <25 kg/m(2), odds ratios (ORs) of poor or fair self-rated health increased among persons with self-reported BMIs of <18.5 (1.57, 95% confidence interval [CI]: 1.31 to 1.89), 25 to <30 kg/m(2) (1.12, 95% CI: 1.04 to 1.20), 30 to <35 kg/m(2) (1.65, 95% CI: 1.50 to 1.81), 35 to <40 kg/m(2) (2.58, 95% CI: 2.21 to 3.00), and > or =40 kg/m(2) (3.23, 95% CI: 2.63 to 3.95); ORs for reporting > or =14 days of poor physical health during the previous 30 days were 1.44 (95% CI: 1.21 to 1.72), 1.04 (95% CI: 0.96 to 1.14), 1.32 (95% CI: 1.19 to 1.47), 1.80 (95% CI: 1.52 to 2.13), and 2.37 (95% CI: 1.90 to 2.94), respectively; ORs for having > or =14 days of poor mental health during the previous 30 days were 1.18 (95% CI: 0.97 to 1.42), 1.02 (95% CI: 0.95 to 1.11), 1.22 (95% CI: 1.10 to 1.36), 1.68 (95% CI: 1.42 to 1.98), and 1.66 (95% CI: 1.32 to 2.09), respectively. DISCUSSION: In the largest study to date, low and increased self-reported BMI significantly impaired health-related quality of life. Particularly, deviations from normal BMI affected physical functioning more strongly than mental functioning.

Potent NK1 antagonism by SR-140333 reduces rat colonic secretory response to immunocyte activation.

The potent neurokinin receptor 1 (NK1) antagonist SR-140333 has previously been shown to reduce castor oil-induced secretion in animal models. The importance of tachykinins in neuroimmune control of secretion and the effect of SR-140333 on key points in this pathway were elucidated in the present study to determine the type of intestinal dysfunction best targeted by this antagonist. Rat colonic secretion and substance P (SP) release were determined in vitro with the use of Ussing chamber and enzyme immunoassay techniques. NK1 receptors played a secretory role as receptor agonists stimulated secretion and SR-140333 antagonized the response to SP response (pK(b) = 9.2). Sensory fiber stimulation released SP and evoked a large secretion that was reduced by 69% in the presence of SR-140333 (10 nM). Likewise, mastocytes also released SP. The subsequent secretory response was reduced by 43% in the presence of SR-140333 (50 nM). SP was also released from granulocytes; however, this did not cause secretion. Functional NK3 receptors were present in the colon as senktide stimulated secretion, an effect that was increased during stress. We conclude that NK3 receptors may play a role in stress-related disorders, whereas NK1 receptors are more important in mast cell/afferent-mediated secretion.

Hypodermoclysis for rehydration in the community.

During 1999 and 2000 the practice development unit of Greater Glasgow Primary Care Trust received an increasing number of requests from community staff for guidance in caring for patients receiving subcutaneous fluids for rehydration. This article describes the process of developing guidelines in order to address the issue. Hypodermoclysis is a relatively safe, simple and cost-effective technique, suitable for use in the community with a range of client groups, e.g. older people or those recovering from recent cardiovascular accidents. Its use in palliative care, however, raises problems in terms of clinical evidence and ethical issues which need to be addressed. Various factors, i.e. products not being licensed for this specific use, staff requests for clinical guidance and the anticipated increasing use of hypodermoclysis for rehydration, all indicated the need for a collaborative approach, address the complexity of issues in the decision-making process and provide clinical guidance with the aim of improving nursing practice and patient outcomes.

DNA extraction from coral reef sediment bacteria for the polymerase chain reaction.

A rapid and effective method for the direct extraction of high molecular weight amplifiable DNA from two coral reef sediments was developed. DNA was amplified by the polymerase chain reaction (PCR) using 16S rDNA specific primers. The amplicons were digested with HaeIII, HinP1I and MspI and separated using polyacrylamide gel electrophoresis and silver staining. The resulting amplified ribosomal DNA restriction analysis (ARDRA) patterns were used as a fingerprint to discern differences between the coral reef sediment samples. Results indicated that ARDRA is an effective method for determining differences within the bacterial community amongst different environmental samples.

Evolutionary change in the use of skills within the district nursing team: a study in two Health Board areas in Scotland.

Grade mix within the district nursing team in the United Kingdom has changed markedly over the last 10 years but the relationship between grade mix and skill mix has received only intermittent research attention. This study adopted an ethnographic approach and aimed to explore the way in which grade and skill are taken into account in the delegation of nursing care. After gaining ethical approval, a total of 76 members of 21 district nursing teams in two areas were observed and interviewed. Delegation practices were found to vary both within and between areas and considerable differences were uncovered in the responsibilities allocated to more junior and unqualified team members. The developing role of nursing auxiliaries is discussed in relation to the role of the G grade sister, resource constraints and the standards of patient care. The paper concludes by arguing that the supervision and leadership role provided by the G grade sister should be fully recognized and safeguarded.

An assessment of the value of intraperitoneal meperidine for analgesia postlaparoscopic tubal ligation.

UNLABELLED: Patients undergoing laparoscopic procedures may experience postoperative pain. The intraperitoneal (IP) administration of drugs is controversial but has proven effective in some studies for the relief of postoperative pain. However, some investigators have not been able to confirm the analgesic efficacy of IP local anesthetics. The administration of IP opioids for the relief of postoperative pain has received little attention. At the end of laparoscopic tubal ligation, 100 patients received 80 mL of 0.125% bupivacaine with 1:200,000 epinephrine IP and 50 mg of meperidine either IP or IM. Postoperative pain scores were measured at rest and with movement. Pain scores were significantly lower in the group receiving the IP meperidine both at rest (P: < 0.01) and with movement (P: < 0.05). We conclude that the combination of intraperitoneal bupivacaine and intraperitoneal meperidine was better than the combination of IP bupivacaine and IM meperidine for postoperative analgesia in patients undergoing laparoscopic tubal ligation. IMPLICATIONS: The combination of bupivacaine and meperidine delivered to the intraperitoneal cavity proved superior to equivalent doses of intraperitoneal bupivacaine and IM meperidine for postoperative pain relief in patients undergoing laparoscopic tubal ligation. Intraperitoneal delivery of analgesia proved effective in this study and merits further study and more widespread use.

Effects of the combination of halothane and serotonin uptake blockers on synaptic transmission in the rat dentate gyrus in vitro.

Although the exact basis of their action remains unknown, volatile agents affect noradrenergic and serotoninergic systems. Imipramine and fluoxetine have documented effects on these neurotransmitter transmission systems. Given the common sites of action of these antidepressants and halothane, we examined their individual and combined effects on tonic excitatory post-synaptic potentials (EPSPs) and frequency dependent blockade in the rat dentate gyrus in vitro. Extracellular recordings of field EPSPs were maintained from the dentate gyrus, in the presence of picrotoxin (100 microM). Stimulation at 30 Hz (200 ms) allowed investigation of frequency dependent blockade. Once a stable equilibrium was established, halothane, imipramine and fluoxetine were administered via the perfusate and recordings were made. Halothane produced a dose dependent reduction in EPSP amplitude (EC50 0.28 mM; n = 12). Imipramine (1-10 microM) potentiated the EPSP amplitude (148.2 +/- 8.2%; imipramine 1 microM; n = 6). Fluoxetine (0.5-10 microM) reduced EPSP amplitude to 83.7 +/- 22.1% of control (n = 6). In the presence of halothane 0.2 mM, imipramine reduced the EPSP amplitude to 56.5 +/- 9.9% of control (imipramine 10 microM; n = 6; p < 0.05 compared with imipramine alone). Halothane (0.2 mM) demonstrated frequency dependent blockade. However, neither imipramine nor fluoxetine showed use dependent inhibition at the doses investigated. When combined with halothane 0.2 mM, fluoxetine 10 microM demonstrated frequency dependent blockade at the sixth pulse in the train compared with controls (13.8 +/- 4.7% vs 38.1 +/- 8.3%; n = 6; p < 0.05). The halothane-imipramine combination did not exhibit use dependent blockade greater than controls. The reversal of imipramine-induced EPSP potentiation by the preapplication of halothane has not been previously reported. It may be due to modulation of noradrenergic transmission by halothane. The frequency dependent blockade produced by the combination of fluoxetine 10 microM and halothane may be mediated by a nonspecific membrane effect on 5-HT uptake. These differing effects underline the broad action of volatile agents on synaptic mechanisms.

Antiproliferative actions of inhalational anesthetics: comparisons to the valproate teratogen.

The antiproliferative potential of the volatile anesthetics isoflurane, enflurane and sevoflurane was determined and compared to the valproate teratogen. The in vitro system employed, a G1 phase proliferative arrest endpoint in C6 glioma, has served previously to discriminate agents with known teratogenic potential in vivo. Based on estimated IC(50) values that were within twice the estimated minimum aveolar concentration value, the rank antiproliferative potency of the inhalational anesthetics employed was isoflurane=enflurane>>sevoflurane. Flow cytometric analysis of growth-arrested cell populations failed to reveal specific accumulation in any cell cycle phase and the lack of a G1 phase-specific effect was confirmed by the absence of a transient, time-dependent sialylation event in synchronized cells. The antiproliferative mechanism of volatile anesthetics, and valproate, was mediated at hydrophobic binding sites, as increasing the hydration sphere of the drug-micelle complex, using the hygroscopic qualities of the dimethylsulfoxide vehicle, completely reversed this effect. Our findings suggest inhalational anesthetics lack the specific in vitro characteristics of the valproate teratogen.

Local interactions and the role of the 6-120 disulfide bond in alpha-lactalbumin: implications for formation of the molten globule state.

Molten globule states are partially folded states of proteins which are compact and contain a high degree of secondary structure but which lack many of the fixed tertiary interactions associated with the native state. A set of peptides has been prepared in order to probe the role of local interactions in the vicinity of the Cys(6)-Cys(120) disulfide bond in stabilizing the molten globule state of human alpha-lactalbumin. Peptides derived from the N-terminal and C-terminal regions of human alpha-lactalbumin have been analyzed using nuclear magnetic resonance, circular dichroism, fluorescence spectroscopy and sedimentation equilibrium experiments. A peptide corresponding to the first helical region in the native protein, residues 1-13, is only slightly helical in isolation. Extending the peptide to include residues 14-18 results in a modest increase in helicity. A peptide derived from the C-terminal 12 residues, residues 112-123, is predominantly unstructured. Crosslinking the N- and C-terminal peptides by the native disulfide bond results in almost no increase in structure and there is no evidence for any significant cooperative structure formation over the range of pH 2.2-11.7. These results demonstrate that there is very little enhancement of local structure due to the formation of the Cys(6)-Cys(120) disulfide bond. This is in striking contrast to peptides derived from the region of the Cys(28)-Cys(111) disulfide.

Memory dysfunction in multiple sclerosis corresponds to juxtacortical lesion load on fast fluid-attenuated inversion-recovery MR images.

BACKGROUND AND PURPOSE: MR imaging is a sensitive diagnostic tool and paraclinical marker of disease activity and prognosis in multiple sclerosis (MS), yet the role of MR imaging of MS is controversial. The aim of this study was to describe the relationship between cognitive function and MS lesion size and position, as shown on comparative images from conventional spin-echo (CSE) and fast fluid-attenuated inversion-recovery (fast FLAIR) MR studies. METHODS: CSE and fast FLAIR sequences consisted of 40 noncontiguous, 3-mm-thick axial sections matched for geometric position in 18 patients with relapsing-remitting MS. Lesions were scored for size, anatomic position, and their comparative appearance on CSE and fast FLAIR images. The neuropsychological assessment tested general psychological performance, memory, and frontal lobe executive function. RESULTS: Fast FLAIR images showed significantly more small (146 versus six) and medium-sized (18 versus four) juxtacortical lesions than did CSE sequences. Small juxtacortical lesions displayed only on fast FLAIR images had a distinctive appearance, suggestive of small areas of perivascular inflammation. The number of these lesions corresponded to reduced performance on the fifth and delayed trials of the Rey Auditory Verbal Learning memory function test. CONCLUSION: Fast FLAIR images show small lesions at the juxtacortical boundary that are not seen on CSE studies. The presence of such lesions correlates with impaired retention of information in memory tasks, which is characteristic of cognitive problems in patients with MS.