Time-course of the uterine response to estradiol-17beta in ovariectomized ewes: expression of angiogenic factors

Uterine expression of angiogenic factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [bFGF]) was evaluated in ovariectomized ewes at 0, 2, 4, 8, 24, 48, or 72 h after estradiol (E2) treatment. Endometrial VEGF mRNA increased more than 5-fold from 0 to 4 h, remained elevated at 8 h, and then declined through 72 h after E2 treatment. In contrast, endometrial bFGF mRNA remained constant from 0 to 4 h, increased 2.2-fold from 4 to 8 h, remained elevated at 24 h, and then declined through 72 h. Immunostaining for VEGF was present in myometrial and endometrial microvessels (arterioles, venules, and/or capillaries) and also in myometrial smooth muscle; the pattern of VEGF immunostaining followed that of mRNA expression, being elevated at 4 and 8 h after E2 treatment. Immunostaining for bFGF was present exclusively in uterine glands; the pattern of bFGF immunostaining also followed that of its mRNA, being elevated at 8 and 24 h after E2. On the basis of these observations, we suggest that VEGF and bFGF are probably important factors responsible for the dramatic uterine microvascular response that occurs 8 to 24 h after E2 treatment in ovariectomized ewes.     

Neuromuscular effects of rocuronium during sevoflurane, isoflurane, and intravenous anesthesia

The potency and time course of action of rocuronium were studied in patients anesthetized with 66% nitrous oxide in oxygen and 1.5 minimum alveolar anesthetic concentration of sevoflurane or isoflurane, or a propofol infusion. Potency was estimated by using the single-bolus technique. Neuromuscular block was measured by stimulation of the ulnar nerve and by recording the force of contraction of the adductor pollicis muscle. The mean (95% confidence limits) of the 50% and 95% effective doses were estimated tobe 142 (129-157) and 265 (233-301) microg/ kg, 165 (146-187) and 324 (265-396) microg/kg, and 183 (163-207) and 398 (316-502) microg/kg during sevoflurane, isoflurane, and propofol anesthesia, respectively (P < 0.05 for sevoflurane versus propofol). The mean +/- SD times to onset of maximal block after rocuronium 0.6 mg/kg were 0.96 +/- 0.16, 0.90 +/- 0.16, and 1.02 +/- 0.15 min during sevoflurane, isoflurane, and propofol anesthesia, respectively. The respective times to recovery of the first response in the train-of-four (TOF) stimulation (T1) to 25% and 90% were 45 +/- 13.1 and 83 +/- 29.3 min, 35 +/- 6.1 and 56 +/- 15.9 min, and 35 +/- 9.2 and 55 +/- 19.4 min. The times to recovery of the TOF ratio to 0.8 were 103 +/- 30.7, 69 +/- 20.4, and 62 +/- 21.1 min, and the 25%-75% recovery indices were 26 +/- 11.7, 12 +/- 5.0, and 14 +/- 6.9 min, respectively. There were no differences among groups in the times for onset of action or to recovery of T1 to 25%. However, the times for recovery of T1 to 90%, TOF ratio to 0.8, and recovery index in the sevoflurane group were all significantly longer compared with the other two groups (P < 0.05, < 0.01, and < 0.01, respectively). We conclude that the effects of rocuronium, especially duration of action, are significantly enhanced during sevoflurane compared with isoflurane and propofol anesthesia. IMPLICATIONS: In routine clinical use, the effects of rocuronium are enhanced by sevoflurane, in comparison with isoflurane and propofol anesthesia, and the recovery is slower. Particular attention should be paid to monitoring of neuromuscular block during sevoflurane anesthesia.     

NMDA receptor-mediated oscillatory activity in the neonatal rat spinal cord is serotonin dependent

The effect of serotonin (5-HT) receptor blockade on rhythmic network activity and on N-methyl--aspartate (NMDA) receptor-induced membrane voltage oscillations was examined using an in vitro neonatal rat spinal cord preparation. Pharmacologically induced rhythmic hindlimb activity, monitored via flexor and extensor electroneurograms or ventral root recordings, was abolished by 5-HT receptor antagonists. Intrinsic motoneuronal voltage oscillations, induced by NMDA in the presence of tetrodotoxin (TTX), either were abolished completely or transformed to long-lasting voltage shifts by 5-HT receptor antagonists. Conversely, 5-HT application facilitated the expression of NMDA-receptor-mediated rhythmic voltage oscillations. The results suggest that an interplay between 5-HT and NMDA receptor actions may be critical for the production of rhythmic motor behavior in the mammalian spinal cord, both at the network and single cell level.     

Accumulation of chylomicron remnants in homozygous subjects with familial hypercholesterolaemia

Despite the obvious differences between the USA and UK health care systems, they share the characteristics of being motivated and managed in relation to cost and process rather than quality (the improved health status of patients). Whilst governments and insurers across the world use the rhetoric of quality, they, as epitomized by the behaviours of UK and USA decision makers, fail to define, measure and implement quality outcome policies. These behaviours are examined and some of their causes are explored briefly. Competition, as designed and used in public (e.g. UK National Health Service) and private (e.g. USA managed care) markets is shown to fail both to identify quality outcome targets and to provide evidence-based and efficient mechanisms to motivate decision makers to be orientated towards continuous quality outcome improvement in health care. A central policy challenge is, consequently, not just the measurement of quality outcomes but also their management into practice.     

Function-sparing surgery for desmoid tumors and other low-grade fibrosarcomas involving the brachial plexus

OBJECTIVE: Low-grade fibrosarcomas and desmoid tumors present a surgical challenge in that they have a strong tendency for local invasion, surgical margins are poorly delineated, and complete resections are difficult. Nowhere is this more evident than in those lesions involving the brachial plexus. We review our experience with these difficult lesions. METHODS: From a prospective database of 2900 patients admitted for treatment of sarcoma between 1982 and 1996, we identified 15 patients with involvement of the brachial plexus by a low-grade fibrosarcoma or desmoid tumor. All patients underwent resection, with 13 of 15 receiving adjuvant radiotherapy. The 15 patients had a mean age at initial operation of 47 years. The male-to-female ratio was 8:7. The mean follow-up period was 65 months (median, 53 mo). RESULTS: Gross total resection was achieved in 12 patients (80%), although 11 of these patients had positive surgical margins. Overall, 64% of the tumors have recurred locally. There were no distant metastases, and no patients died as a result of their disease. One patient died as a result of unrelated cancer. An assessment of the functional outcomes revealed seven patients with normal function or mild neurological deficits and eight who were suffering from significant weakness, debilitation, or chronic pain. One patient required forequarter amputation. CONCLUSION: Surgical resection plus postoperative radiotherapy is the treatment of choice for low-grade fibrosarcomas and desmoid tumors involving the brachial plexus. However, aggressive surgical management with the goal of achieving a gross total resection with negative histological margins can produce unnecessary morbidity. Preserving function should be a primary goal of the operations, although this will be associated with residual disease and will risk local recurrence but rarely death resulting from the disease.     

Prolonged STAT1 activation related to the growth arrest of malignant lymphoma cells by interferon-alpha

Multiple biologic effects of interferon-alpha (IFN-alpha), including cell growth inhibition and antiviral protection, are initiated by tyrosine phosphorylation of STAT proteins. Although this signal pathway has been intensively investigated, the relevance of STAT signal persistence has received scant attention. Using paired isogenic lymphoma cells (Daudi), which either are sensitive or resistant to growth inhibition by IFN-alpha, we found comparable initial tyrosine phosphorylation of multiple STAT proteins; however, the phosphorylation durations and associated DNA-binding activities diverged. Phosphorylation and DNA-binding capacity of STAT1 decreased after 4 to 8 hours in resistant cells, as compared with 24 to 32 hours in sensitive cells, whereas phosphorylation of STAT3 and STAT5b was briefer in both lines. Functional significance of the prolonged STAT1 signal, therefore, was explored by experimental interruption of tyrosine phosphorylation, either by premature withdrawal of the IFN-alpha or deferred addition of pharmacologically diverse antagonists: staurosporine (protein kinase inhibitor), phorbol 12-myristate 13-acetate (growth promoter), or aurintricarboxylic acid (ligand competitor). Results indicated that an approximately 18-hour period of continued STAT1 phosphorylation was associated with growth arrest, but that antiviral protection developed earlier. These differences provide novel evidence of a temporal dimension to IFN-alpha signal specificity and show that duration of STAT1 activation may be a critical variable in malignant cell responsiveness to antiproliferative therapy.     

Magnetic resonance angiography of mesenteric arteries. A review

There has been continued development of MRI techniques for evaluating mesenteric vascular disease. Contrast-enhanced magnetic resonance angiography (MRA) can provide reproducible high resolution, high contrast images of the arterial and venous mesenteric vasculature and may allow detection of segmental ischemia by detection of segmental delayed mesenteric or bowel wall enhancement. Cine phase-contrast MRA can provide additional information about the rate and volume of flow within the major mesenteric arteries and veins. Real-time MRI can provide interactive visualization of the mesenteric vessels in any plane, and with suitable bowel contrast, it can be used to monitor global and segmental small bowel motility. With in vivo MR oximetry, flow independent measurements of the T2 relaxation of blood allow the oxygen saturation of the mesenteric circulation to be determined. These MR techniques can be combined for evaluating both anatomic and functional aspects of the mesenteric circulation.     

Methodology for the study and projection of surgical and anaesthetic workforce

The Australian Medical Workforce Advisory Committee has studied the specialties of anaesthesia, general surgery, orthopaedics, ophthalmology and urology in Australia. A methodology is presented for rationalizing various data sources to establish numbers and characteristics of the existing workforce, for applying a variety of information to establish opinion about current adequacy, to project future needs and to advise the mechanisms to ensure delivery of services. This study emphasizes the importance of the cooperative input of governments, health administrations and professional bodies, careful gathering of fundamental data, the studied application of uneven pieces of evidence, recognition of changes in needs and demands, the overlap of sectors of the medical workforce in service delivery, and the requirement for continued study and monitoring. The current size of the workforce in these surgical specialties is found to be satisfactory overall but with some uneven distribution. The anaesthetic workforce is found to be slightly deficient in number overall. The growth of future demand for these specialties was estimated between 1% and 3% per annum and requirements for increases in trainee numbers to meet these projected future demands are defined.