Early diagnosis of n-hexane–caused neuropathy

n-Hexane neuropathy was studied in 20 workers exposed for prolonged periods to this solvent, and with urinary 2, 5-hexanedione concentrations exceeding the biological exposure index recommended by the American Conference of Governmental Industrial Hygienists (5 mg/L) with a mean of 11.02 mg/L (range 5.3—24.2 mg/L). Although neurological examination did not detect significant anomalies in any of the patients, and the conduction velocity and F waves of all the nerves tested were normal, neurographic studies revealed significant differences in the amplitude of sensory nerve action potentials (SNAP) recorded from the sural (mean 14.0 μV), median (mean 17.3 μV), and ulnar (mean 7.9 μV) nerves when compared with normal values from healthy adults of the same age range, examined under identical conditions. The amplitude of the SNAP in sural and median nerves correlated significantly with the number of years worked. The notable decrease in mean amplitude of the SNAP appeared to reflect the primary neurotoxic effects of 2,5-hexanedione. © 1994 John Wiley & Sons, Inc.     

Union after multiple anterior cervical fusion: 21 cases followed for 1-6 years

With a mean follow-up of 3 (1-6) years, we report on 21 patients who underwent multiple level cervical fusion, using autologous iliac crest grafts. Dis-cectomies were performed in 14 patients and cor-pectomies in another 7. Instrumentation was used in all patients with colectomies and in 2 patients who underwent 2-level and 3-level discectomies. Non-union occurred in 1 patient at 1 level. Graft displacement requiring reoperation was observed in 2 patients with massive corpectomies, in 1 of them as a consequence of trauma. In both patients complete bony fusion was obtained after reoperation and no other complications were observed. We conclude that the success rate with multiple-level fusion is comparable to that of single-level fusion when adequate fixation is achieved.     

Gaining insight into the Clinical Practice Guideline development processes: qualitative study in a workshop to implement the GRADE proposal in Spain

Background  

The GRADE method represents a new approach to grading the quality of evidence and strength of recommendations in the preparation of Clinical Practice Guidelines (CPG). In the context of a pilot study to assess the implementability of the system in Spain, we considered it relevant to gain an insight into the significance of the perceptions and attitudes expressed by the actual experts participating in the system try-out.     

Evaluation of clinical criteria for the acute respiratory distress syndrome in pediatric patients.

OBJECTIVE: The primary goal of this study was to evaluate the validity of the North American-European Consensus Committee (NAECC) definition for acute respiratory distress syndrome (ARDS) in pediatric patients. A secondary aim was to evaluate the threshold value for the PaO2/FiO2 ratio, used to determine which pediatric patients have ARDS. DESIGN: Retrospective cohort study. SETTING: Pediatric intensive care unit. PATIENTS: Pediatric intensive care unit patients who required mechanical ventilation, died, and underwent autopsy between January 1, 1996, and December 31, 2002 (n = 34). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical and chest radiograph information was collected retrospectively through chart review using a standardized data collection tool. Data included the criteria specified in the NAECC definition of ARDS and demographic information. We calculated the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of clinical diagnosis of ARDS compared with a pathologic diagnosis. The threshold value of PaO2/FiO2 was identified by plotting receiver operating characteristics curves and comparing the areas under the curves. The NAECC definition yielded a sensitivity of 80.7% (95% confidence interval 60-92%), specificity of 71.4% (95% confidence interval 30-95), positive predictive value of 91.3% (95% confidence interval 70-98), negative predictive value of 50.0% (95% confidence interval 20-78), and likelihood ratio of 2.82. A PaO2/FiO2 <150 had a slightly higher (but not significantly different) specificity for ARDS than a value >200 (71% vs. 86%, p = .15) without changing sensitivity. CONCLUSIONS: Our study suggests the need for further research with larger number of children to identify an optimal Pao2/Fio2 threshold for identifying ARDS in this population.     

Inhibition of serotonin-induced increase in canine external carotid blood flow by drugs that decrease the sympathetic outflow

1 The present study was designed to analyse the effect of the centrally-acting sympatho-inhibitory drugs, prazosin and ketanserin, on the increase in external carotid blood flow (external CBF) produced by 5-hydroxytryptamine (5-HT) in pentobarbital-anaesthetized dogs. 2 Intracarotid (i.c.) infusions of 5-HT (10 μ g min^?1 during 1 min) produced an increase in external CBF without changes in mean arterial blood pressure or heart rate. This response to 5-HT was dose-dependently blocked by intravenous (i.v.) administration of prazosin (1, 3, 10, 30 and 100 μg kg^?1) or ketanserin (10, 30, 100 and 300 μg kg^?1). 3 Furthermore, 5-HT-induced increase in external CBF was inhibited by either the ganglionic blocking agent, mecamylamine (0.03, 0.1, 0.3, 1, 3 and 10 mg kg^?1), the mixed 5-HT₁-like and 5-HT₂ receptor antagonist, methiothepin (3, 10 and 30 μ g kg^?1) or the 5-HT_1A ligand, spiroxatrine (10, 30, 100 and 300 μg kg^?1). In contrast, the selective 5-HT₂ and 5-HT_1C receptor antagonist, ritanserin (30 and 100 μg kg^?1, i.v.), was unable to block the above response to 5-HT. 4 It is concluded that the inhibition of 5-HT-induced increase in external CBF by prazosin, ketanserin, mecamylamine and spiroxatrine is due to a reduction in the sympathetic tone and not to a blockade of 5-HT receptors.     

Selecting antibodies to detect HER2 overexpression by immunohistochemistry in invasive mammary carcinomas.

There is an increasing clinical demand for HER2 analysis in breast cancer, especially since the release of trastuzumab. The authors assessed the ability of immunohistochemistry to detect HER2 overexpression in invasive mammary carcinomas (IMC) using five antibodies. Paraffin-embedded samples of 86 IMCs (T2N0) were used to compare the immunohistochemical overexpression of HER2 using two polyclonal antibodies (HercepTest [DAKO] and A0485 [DAKO]) and three monoclonal antibodies (CB11 from two different laboratories, Biogenex and Novocastra, and 4D5 [Genentech]). All immunostainings were scored according to the FDA-approved HercepTest recommendations. The HercepTest-positive cases were compared with gene amplification by FISH (Oncor Inform, Ventana). The HercepTest was positive in 31 of the 86 cases (36.1%). The DAKO antibody A0485 was positive in 25 of the 66 (37.8%). Monoclonal antibody 4D5 was positive in only 15 of the 86 cases (17.4%). There was almost total agreement in results between the two CB11 antibodies: 25 of the 86 positive cases (29.1%). All cases positive for CB11 or 4D5 were HercepTest positive. Most of the HercepTest 2+ cases were negative when using either monoclonal antibody. FISH was positive in 19 of the 20 HercepTest 3+ cases and negative in 5 HercepTest 2+ cases. Three CB11-2+ cases showed no amplification by FISH. In three FISH-positive cases the immunohistochemistry showed no overexpression by all antibodies used. These findings suggest that immunohistochemistry may be used reliably as a primary methodology for evaluating HER2; however, the use of polyclonal antibodies may not be adequate to assess HER2 overexpression. CB11, regardless of the manufacturer (Biogenex or Novocastra), showed better concordance with FISH (kappa=0.83) than did the polyclonal antibodies.     

Complications of the cardiopulmonary stress test in patients with depressed left ventricular systolic function.

BACKGROUND: The exercise test has a recognized lower risk of complications when used in the general population and in coronary artery diseased patients, but from a theoretical point of view should have a higher rate of complications when performed in patients with chronic heart failure (CHF). AIMS: To characterize and assess the type and incidence of complications during cardiopulmonary stress test (CPX) in patients with depressed left ventricular systolic function in comparison with a group of patients and individuals with normal function. METHODS: Retrospective analysis of the 334 consecutive CPX performed for risk stratification in 198 patients with a left ventricular ejection fraction below 40% (Group A) and 180 consecutive CPX performed in 78 subjects with normal function (Group B). The two groups were compared with respect to demographic data, CPX parameters and specific complications. Results: Major complications during the tests occurred only in 14 tests of Group A (4.2%, p = 0.012). Non-sustained ventricular tachycardia, <6 beats, occurred in 7 group A and 2 group B tests. The absence of coronary artery disease was the only independent predictor for complications. CONCLUSIONS: Major CPX complications occurred only in patients with impaired left ventricular systolic function. Heart failure patients showed a low probability (around 4%) for complications during CPX, significantly higher and more severe than the risk in the group of patients with normal ventricular function, allowing us to recommend that CPX in patients with heart failure should be performed in a hospital setting under the supervision of a physician with specific training.     

Imaging of acute mesenteric ischemia using multidetector CT and CT angiography in a porcine model

Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols. After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findingsd—compared with pathologic diagnosesd—predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation). Supported by the Karin Grunebaum Research Fellowship, Harvard Medical School (D.E.R.), the German Research Fellowship, German Research Foundation STR 690/1-1 (O.S.), and the Phillip H. Meyers Grant from the Society of Gastrointestinal Radiologists (S.P.T.).     

Analgesia produced by intrathecal administration of the kappa opioid agonist, U-50,488H, on formalin-evoked cutaneous pain in the rat

The antinociceptive activity of the selective k opioid agonist U-50,488H, given intrathecally (i.t.) against chemically induced cutaneous pain in rats, was assessed from cumulative dose-response experiments and the formalin test. Three successive i.t. doses of 5, 10 and 35 nmol of U-50,488H produced a gradual reduction of pain scores which was statistically significant at all observation periods. This effect was antagonized significantly by 3 mg/kg i.p. of the opiate antagonists, naloxone and WIN 44,441-3. The analgesia profile showed a clear dose-response relationship. A dose producing 50% ‘maximum posible analgesia’ of 6.20 nmol (95% confidence interval: 3.05–12.59 nmol) was calculated. The results indicated that cutaneous pain of a chemical/inflammatory nature is highly sensitive to activation of k receptors of the spinal cord dorsal horn.     

Main alkaloids from the Brazilian dendrobatidae frog Epipedobates flavopictus: pumiliotoxin 251D, histrionicotoxin and decahydroquinolines.

Epipedobates flavopictus, Dendrobatidae, is a small aposematic frog found in Brazilian Cerrado bioma. In the present work, we isolated and characterized chemically the most abundant alkaloids present in the cutaneous extract of E. flavopictus. The specimens were collected in Pirenópolis (Goiás, Brazil), their skins were removed and extracted with methanol, and submitted to purification by HPLC and identification by gas chromatography and mass spectrometry. Pumiliotoxin 251D, histrionicotoxin 285Da and two decahydroquinolines, 219A and 243A, were identified. The pumiliotoxin 251D was tested on isolated frog sciatic nerve and on isolated guinea pig ileum muscle. The pumiliotoxin 251D slightly reduced the action potentials amplitude of frog sciatic nerve. The crude skin extract of E. flavopictus and the pumiliotoxin 251D produced rhythmic contractions and increased the muscular tension on isolated guinea pig ileum.