Assessing neuromuscular block at the larynx: the effect of change in resting cuff pressure and a comparison with video imaging in anesthetized humans

Neuromuscular block (NMB) at the larynx has been assessed by measuring the cuff pressure (CP) in an endotracheal tube (ETT) placed between the vocal cords. In this study, we evaluated the decrease in resting cuff pressure (RCP) after the administration of rocuronium and the effect of this decrease on the assessment of NMB, and we compared CP measurement with an alternative technique, video imaging (VI). In 20 patients, NMB was determined at the hand by mechanomyography and at the larynx initially by CP and subsequently by VI, recording images using a fiberoptic bronchoscope via a laryngeal mask. Train-of-four stimuli were applied at both sites. After baseline measurements, the ETT was replaced, and rocuronium was infused to achieve a steady-state 50% (n = 10) or 75% (n = 10) block at the hand. CP measurements were recorded before and after restoration of RCP to prerocuronium pressure, followed by further VI measurements. The mean RCP decreased from 21 +/- 4 to 12 +/- 5 mm Hg after rocuronium. At 50% block at the hand, the CP estimate of block at the larynx with reduced RCP was 62% +/- 18%, and that after restoring RCP was 29% +/- 13%; VI estimated 27% +/- 14% block. At 75% block at the hand, CP and VI estimated 52% +/- 11% and 46% +/- 9% block, respectively (RCP maintained). We conclude that RCP decreases after the administration of rocuronium, that restoring RCP significantly alters CP estimates of NMB, and that VI is in agreement with CP measurement if RCP is maintained at prerelaxant values. Implications: In this study, we show that a muscle relaxant-induced decrease in resting tension at the larynx may confound the assessment of neuromuscular block by cuff pressure measurement. The preliminary data suggest that video imaging may provide a suitable alternative to cuff pressure measurement to assess neuromuscular block at the larynx.     

Identification of 130 kDa cell surface LDL-binding protein from smooth muscle cells as a partially processed T-cadherin precursor

Atypical cell surface lipoprotein-binding proteins of 105 kDa and 130 kDa are present in membranes of vascular smooth muscle cells. We recently identified the 105 kDa protein from human aortic media as T-cadherin, an unusual glycosylphosphatidylinositol (GPI)-anchored member of the cadherin family of cell adhesion proteins. The goal of the present study was to determine the identity of 130 kDa lipoprotein-binding protein of smooth muscle cells. We applied different approaches that included protein sequencing of purified protein from human aortic media, the use of human T-cadherin peptide-specific antisera, and enzymatic treatment of cultured cells with trypsin and GPI-specific phospholipase C. Our results indicate that the 130 kDa protein is a partially processed form of T-cadherin which is attached to the membrane surface of smooth muscle cells via a GPI anchor and contains uncleaved N-terminal propeptide sequence. Our data disclose that, in contrast to classical cadherins, T-cadherin is expressed on the cell surface in both its precursor (130 kDa) and mature (105 kDa) forms.     

Agreement and clinical utility of 2 techniques for measuring cardiac output in patients with low cardiac output

BACKGROUND: The reliability of cardiac output obtained with the bolus technique is a problem. OBJECTIVES: To compare measurements of cardiac output measured with bolus and continuous techniques in patients with low cardiac output and to determine if measurements obtained with the continuous technique increased the number of subsequent clinical decisions. METHODS: In 60 intensive care patients, a nurse recorded a single continuous cardiac output measurement and then obtained the mean of 3 consecutive bolus determinations. The medical records of these 60 patients (experimental group) for the next 48 hours and of 60 other patients with regular or mixed venous oximetry catheters (control group) were reviewed to assess the occurrence of cardiac output events and the frequency of clinical decisions based on the events. RESULTS: Mean cardiac output was 4.46 L/min by the continuous technique and 5.20 L/min by the bolus technique (P = .011) for the experimental group. Median bias between the 2 types of measurements was -0.10 L/min (P = .79). Twenty-three of the pairs (38%) had an absolute percent difference greater than 15%. Of these, 18 (78%) had a higher bolus reading. Treatment decisions per 48 hours were 9.9 for the experimental group and 8.6 for the control group (P = .014). Median length of stay was 2 days less in the experimental group (P = .02), and mean highest cardiac output was 0.81 L/min higher (P = .009). CONCLUSIONS: Measurements of cardiac output determined with the continuous technique may be more precise than measurements determined with the bolus technique. Continuous cardiac output information increases the number of treatment decisions and actions that may shorten hospital length of stay.     

Fibromyalgia, chronic fatigue, and other iatrogenic diagnostic algorithms. Do some labels escalate illness in vulnerable patients?

Contemporary medicine has the sophistication to identify the clinical settings in which the hunt for a diagnosis can be harmful to a patient's health. Which patients are best served by a prolonged search for a cause? Why has the disease-illness paradigm backfired for so many patients? Dr Hadler challenges readers to look at the difficult questions linked with diagnostic labels that might teach patients to stay sick.     

A phase I/II trial of transurethral surgery combined with concurrent cisplatin, 5-fluorouracil and twice daily radiation followed by selective bladder preservation in operable patients with muscle invading bladder cancer

PURPOSE: We describe a protocol designed to evaluate the use of twice daily radiation used together with cisplatin and 5 fluorouracil (5-FU) in the treatment of operable transitional cell carcinoma of the bladder with potential bladder preservation. MATERIALS AND METHODS: A total of 18 consecutive patients with T2-T4a bladder tumors underwent as complete a transurethral resection as possible, which was visibly complete in 14 cases. They then received twice daily radiation and infusion cisplatin and 5-FU during an induction phase. No therapy was given for 3 weeks, following which patients were reevaluated cystoscopically. Cases of clinical complete response by biopsy and cytology were consolidated with further chemotherapy/radiation using the same chemotherapeutic agents and radiation schedule. Patients who had incomplete responses were advised to undergo an immediate radical cystectomy. Of the 18 patients 15 subsequently received 3 cycles of adjuvant chemotherapy, consisting of methotrexate, cisplatin and vinblastine. Median followup for the entire group is 32 months. RESULTS: Of the 18 patients 14 had no detectable tumor after induction therapy. Of the 4 patients with persistent tumor 2 underwent radical cystectomy and 2 refused cystectomy, 1 of whom was treated with partial cystectomy and the other with consolidation chemotherapy/radiation. The actuarial overall survival at 3 years was 83%. The chance of a patient being alive at 3 years with a native bladder was 78%. No patient required cystectomy for hematuria or bladder shrinkage. Three patients in whom superficial tumors developed were treated successfully with bacillus Calmette-Guerin. Small bowel obstruction in 1 case was corrected surgically. CONCLUSIONS: This pilot study demonstrates a high rate of response to this combined chemotherapy/radiation regimen in conjunction with a visibly complete transurethral resection. Reevaluation after a short induction phase allows for the early selection of patients with persistent disease for radical cystectomy.     

Natural killer cell-mediated eradication of neuroblastoma metastases to bone marrow by targeted interleukin-2 therapy

Targeted interleukin-2 (IL-2) therapy with a genetically engineered antidisialoganglioside GD2 antibody-IL-2 fusion protein induced a cell-mediated antitumor response that effectively eradicated established bone marrow and liver metastases in a syngeneic model of neuroblastoma. The mechanism involved is exclusively natural killer (NK) cell-dependent, because NK-cell deficiency abrogated the antitumor effect. In contrast, the fusion protein remained completely effective in the T-cell-deficient mice or immunocompetent mice depleted of CD8+ T cells in vivo. A strong stimulation of NK-cell activity was also shown in vitro. Immunohistology of the leukocytic infiltrate of livers from treated mice revealed a strong staining for NK cells but not for CD8+ T cells. The therapeutic effect of the fusion protein was increased when combined with NK-cell-stimulating agents, such as poly I:C or recombinant mouse interferon-gamma. In conclusion, these data show that targeted delivery of cytokines to the tumor microenvironment offers a new strategy to elicit an effective cellular immune response mediated by NK cells against metastatic neuroblastoma. This therapeutic effect may have general clinical implications for the treatment of patients with minimal residual disease who suffer from T-cell suppression after high-dose chemotherapy but are not deficient in NK cells.     

The role of splenectomy in treating severe aplastic anemia

A hypotensive effect of clonidine in non-narcotized intact and aorta baro-denervated rats is studied under conditions of minimization of stress actions (radiotelemetry) and under standard conditions of direct recording arterial pressure (AP). Direct AP recording is shown to determine an increase in background AP in baro-denervated rats, but not in control rats. An increase in background AP level under conditions of direct recording is not accompanied with decreasing hypotensive effect of clonidine in baro-denervated rats.