Anesthesiologists and acute perioperative stress: a cohort study

Previous studies have indicated that many anesthesiologists exhibit symptoms of chronic stress. There is a paucity of data, however, regarding the existence of acute stress signs among anesthesiologists. Anesthesiologists from three practice settings (n = 38) were studied while they were anesthetizing 203 patients. Heart rate (HR) was recorded continuously and arterial blood pressure (BP) was measured hourly and immediately after each induction. Anxiety levels and salivary cortisol levels were also assessed after each induction. Comparison BP and HR data were obtained from the anesthesiologists during a nonclinical day. We found that anesthesiologists' HR increased during the anesthetic process compared with morning baseline HR (P = 0.008). This HR increase, however, was not clinically significant; the average HR during the anesthetic pro- cess ranged from 80 +/- 12 to 84 +/- 11 bpm. Similarly, although both systolic and diastolic BP after inductions were increased compared with baseline BP (P = 0.001), this increase was not clinically significant. In 9% of the inductions, however, systolic BP exceeded 140 mm Hg, and in 17% of all inductions, diastolic BP exceeded 90 mm Hg. Finally, the average BP of anesthesiologists during a clinical day was not different from the average BP during a nonclinical day (P = 0.9). Self-reported anxiety did not increase significantly after inductions (P = 0.15). An analysis of Holter tapes revealed no rhythm abnormalities and no signs of myocardial ischemia. We conclude that the practice of anesthesiology is associated with minor manifestations of acute physiologic stress during the perioperative process. IMPLICATIONS: Anesthesiologists experience minor psychologic stress while involved in the anesthetic process.     

Mifepristone-misoprostol abortion: a trial in rural and urban Maharashtra,India

As several important policy questions remain regarding the use of medical abortion in developing countries, we investigated the safety, efficacy, and acceptability of mifepristone-misoprostol abortion in the outpatient family planning departments of two urban hospitals and one rural hospital in India. Nine-hundred women (with gestations of < or =63 days in the urban sites and < or =56 days in the rural site) received 600 mg mifepristone followed 48 h later by 400 microg oral misoprostol in the clinic. Four point four percent or fewer urban women and 1.0% rural women were lost to follow-up. Perfect and typical-use failure rates were low at all sites. While rural women reported fewer side effects at all sites, the vast majority of women were satisfied with their medical abortions. Medical abortion can be offered safely, effectively, and acceptably in the outpatient family planning departments of urban and rural hospitals in India.     

Alopecia areata in children: a clinical profile

Alopecia areata (AA) is prevalent among children in Kuwait. In this prospective survey we studied 215 children with AA to determine their clinical and epidemiologic features. Ninety-seven percent of the children were of Arab ancestry. Girls outnumbered boys by a 2.5:1 ratio. The peak age of onset was seen between 2 and 6 years of age with a mean age of onset at 5.7 +/- 2.8 years. A majority of the patients (80.5%) had mild disease and extensive disease (more than 50% hair loss) was seen in 13% of the children. A positive family history of AA was obtained in 51.6% of cases and nail changes were seen in 26.5% of the children. The age of onset, a positive family history of AA, and associated atopic disorders were observed to have no influence on the extent and severity of the disease. The results were compared with those reported elsewhere for this age group.     

Thyroid function,autoantibodies, and HLA tissue typing in children with alopecia areata

A total of 80 Kuwaiti children with alopecia areata (AA), without clinical evidence of thyroid disease, were screened for the presence of thyroid abnormalities, and 50 unrelated children with AA were tissue typed for human leukocyte antigen (HLA) class I and class II antigens. Thyroid abnormalities were detected in 14 children (17.5%). Among these, 11 children (14%) had thyroid autoantibodies. These observations highlight the significance of screening for thyroid abnormalities in children with chronic, recurrent, and/or extensive disease. The Kuwaiti children with AA were observed to have a significant association with HLA B21 (OR 18.850, 95% CI 4.404-80.677), B40 (OR 6.767, 95% CI 1.818-25.181), and HLA B12 (OR 4.833, 95% CI 1.198-19.505) antigens. These findings differed from those reported elsewhere.     

Inhibitory smads and tgf-Beta signaling in glomerular cells

Smad6 and Smad7 are inhibitory SMADs with putative functional roles at the intersection of major intracellular signaling networks, including TGF-beta, receptor tyrosine kinase (RTK), JAK/STAT, and NF-kappaB pathways. This study reports differential functional roles and regulation of Smad6 and Smad7 in TGF-beta signaling in renal cells, in murine models of renal disease and in human glomerular diseases. Smad7 is upregulated in podocytes in all examined glomerular diseases (focal segmental glomerulosclerosis [FSGS], minimal-change disease [MCD], membranous nephropathy [MNP], lupus nephritis [LN], and diabetic nephropathy [DN]) with a statistically significant upregulation in "classical" podocyte-diseases such as FSGS and MCD. TGF-beta induces Smad7 synthesis in cultured podocytes and Smad6 synthesis in cultured mesangial cells. Although Smad7 expression inhibited both Smad2- and Smad3-mediated TGF-beta signaling in podocytes, it inhibited only Smad3 but not Smad2 signaling in mesangial cells. In contrast, Smad6 had no effect on TGF-beta/Smad signaling in podocytes and enhanced Smad3 signaling in mesangial cells. These data suggest that Smad7 is activated in injured podocytes in vitro and in human glomerular disease and participates in negative control of TGF-beta/Smad signaling in addition to its pro-apoptotic activity, whereas Smad6 has no role in TGF-beta response and injury in podocytes. In contrast, Smad6 is upregulated in the mesangium in human glomerular diseases and may be involved in functions independent of TGF-beta/Smad signaling. These data indicate an important role for Smad6 and Smad7 in glomerular cells in vivo that could be important for the cell homeostasis in physiologic and pathologic conditions.     

Phase I Study of Sequential Administration of Topotecan and 5-Fluorouracil in Patients with Advanced Malignancies

Topotecan is a topoisomerase-I inhibitor, a drug that stabilizes a covalent complex of enzymes and causes strand cleavage of DNA. 5-Fluorouracil (5FU) is an antimetabolite that interferes with DNA synthesis. Preclinical studies using human cancer cell line models have shown potential therapeutic synergy between these two drugs by showing the maximum cytolytic effect using sequential 5FU followed by topotecan. In the current study, 5FU was used at a fixed dose of 375 mg/m² given intravenously for five consecutive days on a 28 day cycle. Topotecan was dose-escalated in cohorts of patients from 0.5 to 1.0 mg/m² given intravenously for 5 days after the 5FU dose. Eleven patients were entered at different dose levels. Both hematological and gastrointestinal toxicity were dose limiting. Diarrhea was the dose-limiting toxicity at the dose of 0.75 mg/m² of topotecan. Two cases of grade 4 neutropenia were also observed at this dose level. One patient with small cell lung cancer had a complete response, while one patient with metastatic colorectal cancer had a partial remission. Three other patients had stable disease, lasting between 6 and 8 months. Overall, the regimen was well tolerated. A phase II study using a dose of 5FU at 375 mg/m² followed by topotecan at 0.75 mg/m² intravenously over 5 days every 28 days is recommended.     

Radial artery collateral aneurysm: A rare entity resulting from an unusual etiology

Atherosclerotic occlusive disease of the upper extremity can be a challenging and complex problem for the vascular surgeon. Due to the variety of pathologies that can affect the upper extremity, an accurate diagnosis may be difficult to obtain. We describe the case of a 52-year-old white man who presents with a pulsatile mass on the volar aspect of the right wrist. Arteriography of the aortic arch and right upper extremity revealed an 80% atherosclerotic stenosis at the origin of the right subclavian artery, as well as occlusion of the superficial radial artery. The occlusion resulted in the formation of an aneurysmal collateral, which communicated with the superficial palmar arch. A right carotid-subclavian bypass was necessary to prevent further embolic phenomena. The radial artery aneurysm was treated by resection and primary repair.     

Hepatitis B surface protein docked vesicular carrier for site specific delivery to liver

The intrinsic liver tropism of liposomes can be augmented by the addition of targeting features such as the incorporation of hepatotropic elements of the hepatitis viruses. Hepatitis B virus is known to infect hepatocytes after viremia by asialoglycoprotein receptor mediated uptake. However, the specificity of hepatitis B virus surface protein (HBsAg) towards hepatocytes has confronting reports. In the present study, we evaluated the functional ability of HBsAg to be employed as a ligand for targeting hepatocytes. We prepared (14)C labeled small unilamellar vesicles (SUVs) composed of egg PC/Cholesterol/N-glutarylphosphatidylethanolamine (NGPE) in a 60:30:10 molar ratio. HBsAg was covalently linked to SUVs using a water-soluble carbodiimide (EDC) mediated conjugation with NGPE. In vitro cell binding and uptake studies revealed that bioprotein docked carrier system was efficiently taken up by HepG2 cells by the receptor mediated endocytosis. The biodistribution behaviour of plain and HBsAg coated liposomes was also examined followed by intravenous injection. The study revealed that almost 75% of the radioactivity was recovered in the liver after 4 h of injection that was nearly three-fold greater in magnitude than the plain liposomes. Further, fractionation of liver into liver parenchymal cells (PC) and non-parenchymal cells confirmed the preferential localization of the HBsAg coated liposomal carrier in the parenchymal cells.     

The effects of a subanesthetic dose of ketamine on verbal memory in normal volunteers

Rationale N-methyl-d-aspartate (NMDA) glutamate receptor antagonists have been reported to induce schizophrenia-like symptoms in humans, including memory impairments. Although the NMDA receptor has been shown to impair memory acquisition by disrupting long-term potentiation (LTP), limited research has been done on studying the effects of NMDA antagonists on the post-LTP cascade of events implicated in consolidation as measured by administering the drug after the initial learning experience.Objective The purpose of this experiment was to examine the effect of ketamine on mental status and to identify NMDA antagonist-induced memory deficits by comparing the recall performance of items presented both immediately before and during ketamine infusion.Methods Thirteen normal controls received a 60-min infusion of ketamine in a randomized double-blind, cross-over design. Mental status was evaluated with the Brief Psychiatric Rating Scale and the Clinician-Administered Dissociative States Scale. The first 12-item word list was presented immediately before infusion, and two lists were subsequently presented during the infusion. Verbal memory performance was assessed by measuring the delayed cued recall of each list 30 min after its presentation.Results At the beginning, subjects experienced perceptual and reality distortion symptoms, followed later by mild subjective effects. Ketamine significantly reduced the delayed recall of words presented immediately before, but not during, drug infusion. Ketamine-induced decrements in verbal recall correlated significantly with plasma ketamine levels.Conclusion This study characterizes the behavioral effects associated with ketamine and suggests that ketamine decreases verbal memory performance by interfering with early consolidation processes.