Ilioinguinal and iliohypogastric nerves cannot be selectively blocked by using ultrasound guidance: a volunteer study.

BACKGROUND: Ilioinguinal (IL) and iliohypogastric (IH) nerve blocks are used in patients with chronic postherniorrhaphy pain. The present study tested the hypothesis that our method, previously developed in cadavers, blocks the nerves separately and selectively in human volunteers. METHODS: We blocked the IL and the IH nerves in 16 volunteers in a single-blinded randomized cross-over setting under direct ultrasound visualization, by injecting two times the ED95 volume of 1% mepivacaine needed to block a peripheral nerve. The anaesthetized skin areas were tested by pinprick and marked on the skin. A digital photo was taken. For further analysis, the parameterized picture data were transformed into a standardized and unified coordinate system to compare and calculate the overlap of the anaesthetized skin areas of the two nerves on each side. An overlap <25% was defined as selective block. RESULTS: Fifty nerve blocks could be analysed. The mean volume injected to block a single nerve was 0.9 ml. Using ultrasound, we observed spread from one nerve to the other in 12% of cases. The overlap of the anaesthetized skin areas of the nerves was 60.3% and did not differ after exclusion of the cases with visible spread of local anaesthetic from one nerve to the other. CONCLUSIONS: The IL and IH nerves cannot be selectively blocked even if volumes below 1 ml are used. The most likely explanation is the spread of local anaesthetic from one nerve to the other, although this could not be directly observed in most cases.

Pharmacokinetic parameter sets of alfentanil revisited: optimal parameters for use in target controlled infusion and anaesthesia display systems.

BACKGROUND: In open TCI and anaesthesia display systems, the choice of pharmacokinetic (PK) parameter sets of opioids is clinically relevant. Accuracy and bias of the PK models may be affected by administration mode and the co-administered hypnotic drug. We retrospectively evaluated the performance of eight PK parameter sets for alfentanil in two data sets (infusion and bolus application). METHODS: With the dosing history from two studies in orthopaedic patients anaesthetized with propofol or inhalation anaesthetics the alfentanil plasma concentration over time was calculated with eight PK parameter sets. Median absolute performance error (MDAPE), log accuracy, median performance error (MDPE), log bias, Wobble, and Divergence were computed. Mann-Whitney rank test with Bonferroni correction was used for comparison between bolus and infusion data, repeated measures analysis of variance on ranks was used for comparison among parameter sets. RESULTS: The parameters by Scott (original and weight adjusted) and Fragen had a MDAPE ≤30% and a median log accuracy <0.15 independent of the administration mode, while MDPE was within ±20% and log bias nearly within ±0.1, respectively. The sets by Maitre and Lemmens were within these limits only in the bolus data. All other parameter sets were outside these limits. CONCLUSIONS: In healthy orthopaedic patients, the PK parameters by Scott and by Maitre were equally valid when alfentanil was given as repeated boluses. When given as infusion, the Maitre parameters were less accurate and subject to a significant bias. We cannot exclude that the difference between bolus and infusion is partially because of the different hypnotics used.

Evaluation of a novel needle guide for ultrasound-guided phantom vessel cannulation.

We evaluated a novel, sled-mounted needle guide for ultrasound-guided vessel cannulation. Fifty medical students were randomly assigned to use ultrasound with the sled (sled group, n = 23) or ultrasound without the sled (control group, n = 27) for vessel cannulation in a phantom. For each of 15 attempts we recorded cannulation time and designated a successful cannulation as 1 and a failure as 0. Our primary outcome was the mean overall success rate. The median (IQR [range]) number of successes in the sled group and control group were 15.0 (13.0-15.0 [11.0-15.0]) and 11.0 (9.0-13.0 [6.0-15.0]), respectively (p < 0.001). Cannulation time decreased from the first to the last attempt in the sled group from 7.0 s (6.0-10.0 [4.0-16]) s to 4.0 s (3.0-4.0 [1.0-6.0]) s and in the control group from 35.0 s (27.0-35.0 [11.0-35.0]) s to 7.0 s (5.0-10.0 [3.0-25.0]) s. The sled group demonstrated a shorter cannulation time at each attempt (p < 0.001). The novel sled improved the success rate and efficiency of ultrasound-guided phantom vessel cannulation.

Multimodal therapy for hepatocellular carcinoma: a complementary approach to liver transplantation.

OBJECTIVE: To evaluate the survival benefit of multimodal therapy for the treatment of HCC. BACKGROUND: Orthotopic liver transplantation (OLT) is considered the treatment of choice for selected patients with hepatocellular carcinoma (HCC). However, donor organ shortages and patients whose HCCs exceed OLT criteria require consideration of alternate therapeutic options such as hepatic resection, radiofrequency ablation (RFA), ethanol injection (EI), transarterial chemoembolization (TACE), and chemotherapy (CTX). This study was performed to evaluate the survival benefit of multimodal therapy for treatment of HCC as complementary therapy to OLT. METHODS: A retrospective review was conducted of HCC patients undergoing therapy following multidisciplinary review at our institution from 1996 . 2006 with a minimum of a 2 year patient follow-up. Data were available on 247/252 patients evaluated. Relevant factors at time of diagnosis included symptoms, hepatitis B (HBV) and C (HCV) status, antiviral therapy, Child-Pugh classification, portal vein patency, and TNM staging. Patients underwent primary treatment by hepatic resection, RFA, EI, TACE, CTX, or were observed (best medical management). Patients with persistent or recurrent disease following initial therapy were assessed for salvage therapy. Survival curves and pairwise multiple comparisons were calculated using standard statistical methods. RESULTS: Mean overall survival was 76.8 months. Pairwise comparisons revealed significant mean survival benefits with hepatic resection (93.2 months), RFA (66.2 months), and EI (81.1 months), compared with TACE (47.4 months), CTX (24.9 months), or observation (31.4 months). Shorter survival was associated with symptoms, portal vein thrombus, or Child-Pugh class B or C. HCV infection was associated with significantly shorter survival compared with HBV infection. Antiviral therapy was associated with significantly improved survival in chronic HBV and HCV patients only with earlier stage disease. CONCLUSION: Multimodal therapy is effective therapy for HCC and may be used as complementary treatment to OLT.

Perioperative analysis of laparoscopic versus open liver resection.

BACKGROUND: Over the past decade there has been an increasing trend toward minimally invasive liver surgery. Initially limited by technical challenges, advances in laparoscopic techniques have rendered this approach safe and feasible. However, as health care costs approach 50% of some provincial budgets, surgical innovation must be justifiable in costs and patient outcomes. With introduction of standardized postoperative liver resection guidelines to optimize patient hospital length of stay, the advantages of laparoscopic liver resection (LLR) compared with open liver resection (OLR) measured by perioperative outcomes and resource utilization are not well defined. It remains to be established whether LLR is superior to OLR by these measurements. METHODS: Eighteen LLRs performed at the Vancouver General Hospital from 2005 to 2007 were prospectively analyzed. These data were compared with an equivalent group of 12 consecutive OLRs undertaken immediately prior to the introduction of LLR. Outcomes were evaluated for differences in perioperative morbidity, hospital length of stay, and operative costs. RESULTS: There were no differences between LLRs and OLRs in demographics, pathology, cirrhosis, tumour location or extent of resection. There were no deaths. LLRs had significantly decreased intraoperative blood loss (287 ml versus 473 ml, p = 0.03), postoperative complications (6% versus 42%, p = 0.03), and length of stay (4.3 versus 5.8 days, p = 0.01) compared with OLRs. There were no differences in operating time for LLRs compared to OLRs (135 min versus 138 min, respectively), total time in the operating theatre (214 min versus 224 min), or costs related to stapler/trocar devices (CA $1267 versus CA $1007). CONCLUSIONS: LLR is associated with decreased morbidity and decreased resource utilization compared with OLR. Perioperative patient outcomes and cost-effectiveness justify LLR despite introduction of standardized postoperative liver resection guidelines and decreased length of stay for OLR.

Late acute celiac and hepatic artery thrombosis with portal vein thrombosis resulting in hepatic infarction 12 years post orthotopic liver transplantation.

Hepatic artery thrombosis (HAT) is relatively infrequent, but possibly a devastating complication of orthotopic liver transplantation (OLT). It often requires urgent retransplantation. Two main forms of HAT are recognized as early and late HAT (diagnosis within or after 30 days following LT). Early HAT typically results in graft failure. Late HAT features biliary obstruction, cholangitis, and hepatic abscess formation. We report here the case of a patient of Wilson's disease who presented twelve years post-liver transplant symptoms typical of acute HAT and hepatic infarction. On diagnostic imaging, celiac axis and hepatic artery were thrombosed, resulting in ischemic necrosis of the left hepatic lobe. The resulting sepsis and transient hepatic insufficiency were managed conservatively, and repeat OLT was avoided. The patient remains stable more than one year later. To the best of our knowledge this case report is unique in the literature for the unusually long interval between OLT and late acute HAT, as well as celiac and portal vein occlusion. The acute presentation of sub massive hepatic necrosis is also uncharacteristic of late HAT and more typical of acute HAT. This report describes our experience in managing this and a literature review of the topic.

Eutectic modification by ternary compound cluster formation in Al-Si alloys.

Al-alloys with Si as the main alloying element constitute the vast majority of Al castings used commercially today. The eutectic Si microstructure in these alloys can be modified from plate-like to coral-like by the addition of a small amount of a third element to improve ductility and toughness. In this investigation the effects of Eu and Yb are studied and their influence on the microstructure is compared to further understand this modification. The two elements impact the alloy differently, where Eu modifies Si into a coral-like structure while Yb does not. Atom probe tomography shows that Eu is present within the Si phase in the form of ternary compound Al2Si2Eu clusters, while Yb is absent in the Si phase. This indicates that the presence of ternary compound clusters within Si is a necessary condition for the formation of a coral-like structure. A crystallographic orientation relationship between Si and the Al2Si2Eu phase was found, where the following plane normals are parallel: 011Si//0001Al2Si2Eu, 111Si//6[Formula: see text]10Al2Si2Eu and 011Si//6[Formula: see text]10Al2Si2Eu. No crystallographic relationship was found between Si and Al2Si2Yb. The heterogeneous formation of coherent Al2Si2Eu clusters inside the Si-phase is suggested to trigger the modification of the microstructure.

Ion mass and energy selective hyperthermal ion-beam assisted deposition setup.

For the synthesis of high-quality thin films, ion-beam assisted deposition (IBAD) is a frequently used technique providing precise control over several substantial film properties. IBAD typically relies on the use of a broad-beam ion source. Such ion sources suffer from the limitation that they deliver a blend of ions with different ion masses, each of them possessing a certain distribution of kinetic energy. In this paper, a compact experimental setup is presented that enables the separate control of ion mass and ion kinetic energy in the region of hyperthermal energies (few 1 eV - few 100 eV). This ion energy region is of increasing interest not only for ion-assisted film growth but also for the wide field of preparative mass spectrometry. The setup consists of a constricted glow-discharge plasma beam source and a tailor-made, compact quadrupole system equipped with entry and exit ion optics. It is demonstrated that the separation of monoatomic and polyatomic nitrogen ions (N+ and N2+) is accomplished. For both ion species, the kinetic energy is shown to be selectable in the region of hyperthermal energies. At the sample position, ion current densities are found to be in the order of 1 µA/cm2 and the full width at half maximum of the ion beam profile is in the order of 10 mm. Thus, the requirements for homogeneous deposition processes in sufficiently short periods of time are fulfilled. Finally, employing the described setup, for the first time in practice epitaxial GaN films were deposited. This opens up the opportunity to fundamentally study the influence of the simultaneous irradiation with hyperthermal ions on the thin film growth in IBAD processes and to increase the flexibility of the technique.

Novel lingual retainer created using CAD/CAM technology: evaluation of its positioning accuracy.

OBJECTIVES: Permanent retention is currently the method of choice to stabilize orthodontic treatment results. Frequently, permanent retention schemes are adopted to prevent posttreatment changes in the esthetic zone of the anterior teeth. With increasingly prolonged times of intraoral device use, and retention to be provided in the maxilla despite limited space, the demands placed on well-planned and precise retainer positioning are becoming more exacting. The aim of the present study was to analyze the intraoral precision of lingual retainers made using computer-aided design and machining (CAD/CAM). MATERIALS AND METHODS: A custom manufacturer (Retaintechnology; Cologne, Germany) employing innovative CAD/CAM technology was commissioned to fabricate 16 lingual retainers. Following intraoral insertion using the manufacturer's recommended transfer system, impressions of the intraoral situations were taken and scanned for digitization. On this basis, the intraoral retainer positions were compared to the preceding virtual setups by superimposition with the manufacturer's datasets. Three-dimensional processing software (Geomagic Qualify 2012; Geomagic) was used to analyze the retainers, based on a total of 80 interproximal sites, for deviations from their planned positions along the horizontal (x-), sagittal (y-), and vertical (z-) axes. These deviations of the achieved from the intended positions were considered clinically relevant if ≥ 0.5 mm and, based on this premise, were subjected to a t-test with statistical software (Prism; GraphPad). RESULTS: The intraoral retainer positions were found to correlate closely with the preceding virtual setups (i.e., the positions as they had been planned by the custom manufacturer). Positional deviations were significantly less than 0.5 mm. They were very small in the horizontal and sagittal planes and moderately larger in the vertical plane. CONCLUSION: Highly precise intraoral results may be achieved by transferring three-dimensional virtual setups for lingual retainers to the actual patients. This CAD/CAM strategy of making retainers can offer high predictability even in anatomically demanding regions and in the presence of limited space.

Vascular endothelial growth factor in CSF: a biological marker for carcinomatous meningitis.

OBJECTIVE: To determine the value of vascular endothelial growth factor (VEGF) in CSF as a marker for carcinomatous meningitis (CM). METHODS: The concentration of VEGF was measured by ELISA in matched samples of CSF and serum collected from 162 patients. These included patients with solid tumors with CM (n = 11) or brain metastases without concomitant CM (n = 12), paraneoplastic neurologic syndromes (n = 4), viral (n = 15) and bacterial (n = 20) meningitis, and a variety of non-neoplastic and noninfectious neurologic diseases (n = 100). Using CSF/serum albumin ratios, the VEGF index was calculated to estimate the proportion of intrathecally produced VEGF. Immunohistochemical staining for VEGF was performed in a brain metastasis from a mammary carcinoma associated with CM. RESULTS: High VEGF levels (median 6,794.8 pg/mL) were found in CSF of all patients with CM, whereas VEGF levels in matched sera were comparable to other disease groups. In patients with CM, the concentration of VEGF in CSF decreased significantly following antineoplastic treatment. In CSF samples from patients with brain metastases without concomitant CM, VEGF was not detectable. Median VEGF concentration in CSF from patients with acute bacterial meningitis was 38.6 pg/mL, with only 9 of these 17 patients showing detectable VEGF levels in CSF. The VEGF indices in patients with bacterial meningitis were significantly lower than in tumor patients with CM (<22.8 versus >62.3), suggesting that the proportion of intrathecally produced VEGF is much higher in patients with CM as compared with patients with bacterial meningitis. Patients without neoplastic or infectious neurologic disorders consistently showed VEGF levels in CSF below the assay detection limit of 25 pg/mL. Immunohistochemistry revealed strong cytoplasmic staining for VEGF in a metastatic lesion from breast cancer infiltrating the meninges. CONCLUSION: In patients with carcinomatous meningitis, significant amounts of VEGF are released into CSF. This study yields preliminary evidence that VEGF in CSF may be a useful biologic marker for both the diagnosis and evaluation of treatment response in carcinomatous meningitis.

Synthesis and in vitro efficacy of transferrin conjugates of the anticancer drug chlorambucil.

One strategy for improving the selectivity and toxicity profile of antitumor agents is to design drug carrier systems employing soluble macromolecules or carrier proteins. Thus, five maleimide derivatives of chlorambucil were bound to thiolated human serum transferrin which differ in the stability of the chemical link between drug and spacer. The maleimide ester derivatives 1 and 2 were prepared by reacting 2-hydroxyethylmaleimide or 3-maleimidophenol with the carboxyl group of chlorambucil, and the carboxylic hydrazone derivatives 5-7 were obtained through reaction of 2-maleimidoacetaldehyde, 3-maleimidoacetophenone, or 3-maleimidobenzaldehyde with the carboxylic acid hydrazide derivative of chlorambucil. The alkylating activity of transferrin-bound chlorambucil was determined with the aid of 4-(4-nitrobenzyl)pyridine (NBP) demonstrating that on average 3 equivalents were protein-bound. Evaluation of the cytotoxicity of free chlorambucil and the respective transferrin conjugates in the MCF7 mammary carcinoma and MOLT4 leukemia cell line employing a propidium iodide fluorescence assay demonstrated that the conjugates in which chlorambucil was bound to transferrin through non-acid-sensitive linkers, i.e., an ester or benzaldehyde carboxylic hydrazone bond, were not, on the whole, as active as chlorambucil. In contrast, the two conjugates in which chlorambucil was bound to transferrin through acid-sensitive carboxylic hydrazone bonds were as active as or more active than chlorambucil in both cell lines. Especially, the conjugate in which chlorambucil was bound to transferrin through an acetaldehyde carboxylic hydrazone bond exhibited IC50 values which were approximately 3-18-fold lower than those of chlorambucil. Preliminary toxicity studies in mice showed that this conjugate can be administered at higher doses in comparison to unbound chlorambucil. The structure-activity relationships of the transferrin conjugates are discussed with respect to their pH-dependent acid sensitivity, their serum stability, and their cytotoxicity.

Increased calpain I-mediated proteolysis, and preferential loss of dephosphorylated NF200, following traumatic spinal cord injury.

We investigated the hypothesis that the Ca2+-activated protease calpain is involved in the pathophysiology of spinal cord injury, and is linked to the proteolytic degradation of cytoskeletal proteins. We report here that levels of calpain I (mu-calpain)-mediated spectrin breakdown products are increased by 15 min post-injury, with peak levels reached by 2 h post-injury. The dephosphorylated form of the neurofilament protein NF200 is substantially lost over the same time-period. A 35-g compressive injury was applied to the midthoracic rat spinal cord for 1 min, and animals were killed at 15 min, 1, 2, 4, 8, 16, and 24 h post-injury. Calpain I-mediated spectrin breakdown products accumulated post-injury, with peak levels reached at 2 h. Secondly, we have demonstrated a progressive loss of the 200,000 mol. wt neurofilament protein NF200, a cytoskeletal calpain substrate, which began within 1-2 h post-injury. Densitometric analyses confirmed that loss of NF200 is a substrate-specific phenomenon, since (i) dephosphorylated NF200 was preferentially lost while phosphorylated NF200 was relatively spared, and (ii) actin, which is not a substrate for calpain, was relatively spared following spinal cord injury. Finally, we demonstrated calpain I-mediated spectrin breakdown within NF200-positive neuronal processes post-injury. We conclude that the accumulation of spectrin breakdown products is temporally and spatially correlated with loss of dephosphorylated NF200 after spinal cord injury.

Evaluation of the Sysmex R-1000. An automated reticulocyte analyzer.

The new fully automated reticulocyte analyzer, Sysmex R-1000 (TOA Medical Electronics, Kobe, Japan), was evaluated for its routine use in the Hematological Laboratory at the University Hospital Basel, Switzerland. The operating characteristics, such as within-run precision, linearity, and carryover, fulfilled the manufacturer's specifications and are excellent. Correlation with the standard method, manual reticulocyte counting, is linear for normal and high values. For low reticulocyte counts the regression points show a deviation from their linearity. An absolute zero value is not obtained by the R-1000. The R-1000 measures total RNA content of each cell and expresses the value as low fluorescence ratio (LFR), medium fluorescence ratio (MFR), and high fluorescence ratio (HFR). The analysis of this ratio resolves the problem of zero reticulocytes: A fraction of less than 0.002 (0.2%) with an LFR of 100% represents aplasia; a shift of the intensity of fluorescence to HFR heralds regeneration. Results of samples stored at room temperature remain stable and within the range of the within-run precision for up to 12 hours, when stored at 5 degrees C for more than 48 hours. The authors conclude that the R-1000 is easy to operate, fulfills the criteria for accuracy and precision, and is highly suitable for daily routine use in a large central hematologic laboratory.

Management of of arteriosclerotic aneurysm of the innominate artery.

Arteriosclerotic aneurysm of the innominate artery is an unusual lesion. A review of the literature has revealed many approaches to this problem in the past, but the mortality rate has remained significant and serious complications have been frequent. Computerized axial tomography and noninvasive cerebrovascular methods can be useful in managing this lesion. Vein grafts from the ascending aorta to the common carotid and subclavian arteries were used to revascularize a patient following resection of an innominate aneurysm.

Mitral valve reconstruction in the elderly population.

The technique, efficacy, and long-term results of mitral valve reconstruction have been well demonstrated and reported by Carpentier and other investigators. However, most of the results reported have been in patients aged less than 65 years. Between April 1985 and September 1988, we performed mitral valve reconstruction in 176 patients using Carpentier's classification and technique for repair. Ages ranged from 15 to 86 years (mean age, 63 years). Of the repairs, 96/176 (55%) had concomitant cardiac procedures. Patients aged 65 years or more accounted for 52% (92/176) of the population and 35% (65/176) were more than 70 years old. Hospital mortality (30 day) was 4% (4/84) in the group aged less than 65 years. Hospital mortality for the group aged more than 65 years was 12% (11/92), compared with an overall 8.5% mortality. These results suggest an increased morbidity with mitral valve repair in the patients aged more than 65 years, but this group represents an even higher risk group with mitral valve replacement.

In vitro and in vivo efficacy of acid-sensitive transferrin and albumin doxorubicin conjugates in a human xenograft panel and in the MDA-MB-435 mamma carcinoma model.

Acid-sensitive transferrin and albumin conjugates with doxorubicin have recently been developed with the aim of circumventing the systemic toxicity and improving the therapeutic efficacy of this anticancer agent. The in vitro activity of two acid-sensitive transferrin and albumin doxorubicin conjugates and free doxorubicin was evaluated in twelve human tumour xenografts using a clonogenic assay. The inhibitory effects and the activity profile of the conjugates was, in general, comparable to that of doxorubicin (mean IC(70) -value for doxorubicin approximately 0.1 microM and 0.1 - 0.4 microM for the conjugates). Subsequently, the efficacy of an acid-sensitive transferrin and albumin doxorubicin conjugate, which both incorporated a phenylacetyl hydrazone bond as a predetermined breaking point, was evaluated in the xenograft mamma carcinoma model MDA-MB-435 in comparison to free doxorubicin (dose, i.v.: 2 x 4, 8 and 12 mg/kg). The conjugates showed significantly reduced toxicity (reduced lethality and body weight loss) with a concomitantly stable or slightly improved antitumour activity compared to free doxorubicin. At the dose of 12 mg/kg mortality was unacceptably high in the doxorubicin treated group ( approximately 80%); in contrast, no mortality was observed with the conjugate treated animals with body weight loss < 10 %. In a further experiment, therapy with the acid-sensitive doxorubicin albumin conjugate at 3 x 12 mg/kg in the MDA-MB-435 model resulted in a significantly improved antitumour activity over free doxorubicin at its optimal dose of 2 x 8 mg/kg. In conclusion, acid-sensitive transferrin and albumin doxorubicin conjugates can be administered at higher doses than free doxorubicin in nude mice models with a concomitant improvement in antitumour activity. Interestingly, there is no pronounced difference between identically constructed transferrin and albumin doxorubicin conjugates with regard to in vitro or in vivo efficacy.

Transferrin conjugates of doxorubicin: synthesis, characterization, cellular uptake, and in vitro efficacy.

One strategy for improving the antitumor selectivity and toxicity profile of antitumor agents is to design drug carrier systems employing suitable carrier proteins. Thus, thiolated human serum transferrin was conjugated with four maleimide derivatives of doxorubicin that differed in the stability of the chemical link between drug and spacer. Of the maleimide derivatives, 3-maleimidobenzoic or 4-maleimidophenylacetic acid was bound to the 3'-amino position of doxorubicin through a benzoyl or phenylacetyl amide bond, and 3-maleimidobenzoic acid hydrazide or 4-maleimidophenylacetic acid hydrazide was bound to the 13-keto position through a benzoyl hydrazone or phenylacetyl hydrazone bond. The acid-sensitive transferrin conjugates prepared with the carboxylic hydrazone doxorubicin derivatives exhibited an inhibitory efficacy in the MDA-MB-468 breast cancer cell line and U937 leukemia cell line comparable to that of the free drug (employing the BrdU (5-bromo-2'-deoxyuridine) incorporation assay and tritiated thymidine incorporation assay, respectively, IC50 approximately 0.1-1 mM), whereas conjugates with the amide derivatives showed no activity. Furthermore, antiproliferative activity of the most active transferrin conjugate (i.e. the conjugate containing a benzoyl hydrazone link) was demonstrated in the LXFL 529 lung carcinoma cell line employing a sulforhodamine B assay. In contrast to in vitro studies in tumor cells, cell culture experiments performed with human endothelial cells (HUVEC) showed that the acid-sensitive transferrin conjugates of doxorubicin were significantly less active than free doxorubicin (IC50 values approximately 10-40 higher by the BrdU incorporation assay), indicating selectivity of the doxorubicin-transferrin conjugates for tumor cells. Fluorescence microscopy studies in the MDA-MB-468 breast cancer cell showed that free doxorubicin accumulates in the cell nucleus, whereas doxorubicin of the transferrin conjugates is found localized primarily in the cytoplasm. The differences in the intracellular distribution between transferrin-doxorubicin conjugates and doxorubicin were confirmed by laser scanning confocal microscopy in LXFL 529 cells after a 24 h incubation that revealed an uptake and mode of action other than intercalation with DNA. The relationship between stability, cellular uptake, and cytotoxicity of the conjugates is discussed.

Subtraction procedure for the registration of tissue perfusion with Doppler ultrasound.

Tissue perfusion, i.e., in muscles or parenchymatous organs, is of both physiological and pathophysiological interest. The measurement of tissue perfusion is an unsolved problem. The Doppler ultrasound method is well suited to this purpose. However, measurements using this technique may be disturbed by movements or vibrations such as heart motion, muscle trembling or vibration of the subsoil (i.e. the examination table). These interfering movements produce Doppler frequencies in the same frequency range as slowly flowing erythrocytes, causing artifacts to appear in the measured data. The goal of this project was to suppress such artifacts with the help of a subtraction procedure. The mathematical theory of this subtraction procedure and its implementation in a newly developed two channel Doppler system are presented. This system was successfully tested on a phantom which is able to generate flow and movement artifacts. Preliminary measurements in the forearms of volunteers showed that movement artifacts can be at least partially suppressed.

Effects of intravenous lidocaine and/or esmolol on hemodynamic responses to laryngoscopy and intubation: a double-blind, controlled clinical trial.

STUDY OBJECTIVES: To evaluate the efficacy of intravenous lidocaine and two doses of esmolol for attenuating the cardiovascular responses to laryngoscopy and intubation, and to assess whether a combination of both drugs is more effective than either drug alone. DESIGN: Randomized, prospective, double-blind, placebo-controlled study. SETTING: University hospital. PATIENTS: 90 ASA status I and II normotensive women scheduled for elective gynecologic procedures with general anesthesia. INTERVENTIONS: Induction of anesthesia was standardized for all patients. The first group received lidocaine 1.5 mg/kg (Group LID); the second and third groups received esmolol 1 mg/kg and 2 mg/kg, respectively (Groups E1 and E2, respectively); the fourth group received lidocaine 1.5 mg/kg and esmolol 1 mg/kg (Group LID-E1); the fifth group received lidocaine 1.5 mg/kg and esmolol 2 mg/kg (Group LID-E2); the sixth group received saline as a placebo (Group PLAC). MEASUREMENTS AND MAIN RESULTS: Systolic blood pressure and heart rate (HR) were recorded before induction, before injection of the first test drug, immediately before laryngoscopy, and 1, 2, and 5 minutes following intubation. Duration of laryngoscopy was recorded. Only patients receiving placebo had increased HR values after intubation compared with baseline values (p < 0.05). The proportion of patients with a maximum HR exceeding 90 beats/min was significantly higher in the placebo group (8 of 15 patients) than in both esmolol groups (E1 2 of 15; E2 2 of 15) (p < 0.05). Systolic blood pressure values after tracheal intubation did not differ among groups except for those receiving the combinations of lidocaine and esmolol, and they had significantly lower blood pressure (BP) values compared with placebo (p < 0.05). CONCLUSIONS: Esmolol 1 to 2 mg/kg is reliably effective in attenuating HR response to tracheal intubation. Neither of the two doses of esmolol tested nor that of lidocaine affected the BP response. Only the combination of lidocaine and esmolol attenuated both HR and BP responses to tracheal intubation.

[Weaning of young smokers using a transdermal nicotine patch]. / Entwöhnung junger Raucher mit Hilfe eines transdermalen Nikotinpflasters.

To assess efficacy and tolerance of a transdermal nicotine system (TNS) as adjuvant to tobacco withdrawal, 112 young, nicotine-dependent cigarette smokers were treated for nine weeks with TNS (n = 56) or placebo (n = 56). Initial doses of nicotine (21 or 14 mg/24 h) were based on previous smoking habits and stepwise reduced to 7 mg/24 h if abstinence was achieved during medication. After treatment, 39.3% of the TNS users were abstinent versus 19.6% on placebo (p less than 0.05). The craving for cigarettes diminished steadily, but not more significantly on TNS medication. Tenseness, difficulty in concentration and feelings of hunger were consistently and in part significantly lessened in the TNS group. The other withdrawal symptoms were not influenced by TNS treatment. Nine-month follow-up cotinine-verified abstinence rates were 12.5% in the TNS and 3.6% in the placebo group (n. s.). Transient mild or moderate erythema at the application site appeared in 20% of the TNS and 6.3% of the placebo group, and 7.1% of the TNS users dropped out because of severe localized erythema. Other mild, transient, systemic side effects reported by 33.9% of the TNS and 26.8% of the placebo users (n. s.) did not lead to drop-outs.