Serum alanine aminotransferase has limited predictive value for liver disease in chronic hepatitis C.

OBJECTIVES: Serum alanine aminotransferase (ALT) levels are sometimes used to identify patients with progressive liver disease in chronic hepatitis C. We assessed the predictive value of serum ALT at various cut-off levels, for the identification of liver disease severity. PATIENTS AND METHODS: This cross sectional study was carried out at Ziauddin University and Pakistan Medical Research Council, Karachi. Liver biopsy specimens were staged and graded according to METAVIR scoring system. Identification of overall significant liver disease (F2 or A2 and above) was the primary outcome variable. Diagnostic value of ALT was assessed through receiver operating characteristic (ROC) curve analysis. RESULTS: Out of 98 patients, 42 (43%) had significant fibrosis and 26 (27%) had significant inflammatory activity. Overall significant liver disease was present in 46 (47%) patients of which 13 had widespread fibrosis. Area under the ROC curve for overall significant disease was 0.727 (95% CI 0.627-0.826). A clinically acceptable cut off level to rule out presence of clinically significant disease was found to be ≤ 20 U/L. This low level of ALT was present in 13 (13%) patients. At this cut off, sensitivity was 96%, specificity was 19%, positive predictive value was 49% and negative predictive value was found to be 85%. CONCLUSIONS: Serum ALT level of ≤ 20 U/L can reliably exclude significant liver disease. Values of ALT above 20 U/L do not reliably differentiate between minimal and significant disease.

Development and Validation of a RPLC Method for the Determination of 2-Phenoxyethanol in Senselle Lubricant Formulation.

A new and simple reversed-phase liquid chromatographic method has been developed and validated for the determination of 2-phenoxyethanol preservative (0.3%, w/w) in senselle lubricant formulation. The separation was achieved with acetonitrile-tetrahydrofuran-water (21:13:66, v/v/v) as mobile phase, a C(8) column, and UV detection at 258 nm. The calibration curve is linear (r(2)= 0.9999) from 20-140% of the analytical concentration of 0.75 mg/ml. The mean percent relative standard deviation values for intra- and inter-day precision studies are <1%. The recovery of 2-phenoxyethanol ranged between 99.76 and 100.03% from lubricant formulation. The limits of detection and quantitation are determined to be 0.094 and 0.15 mg/ml, respectively. The method was found to be robust and can be successfully and reliably used to determine the 2-phenoxyethanol preservative content of marketed formulations.

Variability of duration of action of neuromuscular-blocking drugs in elderly patients.

BACKGROUND: Steroid-based, non-depolarizing neuromuscular-blocking (NMB) drugs (e.g. rocuronium, vecuronium) are characterized by organ-dependent elimination and significantly longer durations of action in elderly compared to young patients. Cisatracurium is a benzylisoquinolinium NMB drug with a duration of action not altered by ageing. The objective of the study was to determine if elderly patients had less variability in duration of action with 2 x ED95 of cisatracurium compared to equipotent doses of rocuronium or vecuronium. METHODS: Informed consent was obtained from 66 elderly patients with normal renal and liver function. Preoperative midazolam (1 mg) was given IV. The anaesthestic induction was with 5 mg kg(-1) thiopental and 2 microg kg(-1) fentanyl. The patients received 0.6 mg kg(-1) rocuronium, 0.1 mg kg(-1) vecuronium or 0.1 mg kg(-1) cisatracurium. Anaesthetic maintenance was with sevoflurane in oxygen/nitrous oxide. Neuromuscular-blocking duration of action was defined as the return of T1 twitch height to 25% of control. Variability was determined by subtracting the actual duration of action from the mean duration of action for each drug. RESULTS: The durations of action (range, min) were: cisatracurium, 37-81; vecuronium, 35-137; and rocuronium, 33-119. The median of the variability of duration was significantly less with cisatracurium (7 min) compared to vecuronium (18 min) and rocuronium (18 min) (P < 0.05). CONCLUSION: When used with sevoflurane/N(2)O, there was a two-fold greater variability of duration of neuromuscular blockade in elderly patients receiving rocuronium or vecuronium compared with cisatracurium.

Hematologic and cytogenetic findings in eleven chronic myelogenous leukemia patients treated with imatinib mesylate at a tertiary care hospital.

OBJECTIVE: To evaluate the response of Imatinib mesylate in patients with myeloid leukemia in chronic accelerated and blast phase. PATIENTS AND METHODS: Eleven patients with established diagnosis of chronic myeloid leukemia were treated with Imatinib mesylate. Adverse events were documented with regular follow ups. Hematological and cytogenetic responses were assessed according to established criteria. Patients with zero percent Philadelphia positive metaphases were labeled as complete cytogenetic response while patients with 1% to 35% Philadelphia positive metaphases were termed as partial responders. RESULTS: Of 11 cases there were 7 males and 4 females with a mean age of 39.5 years and median age 51 years (range 21-69). Male to female ratio was 7:4. Median follow-up was 34 weeks (range 8-78). Four patients were in blast crisis, 1 in accelerated phase and remaining six patients were in chronic phase. All patients achieved hematological response. Cytogenetic response was present in six patients, 3 were responders and the remaining were non responders. Two patients achieved complete cytogenetic response and one patient had partial cytogenetic response. Both patients with complete cytogenetic response relapsed in twelve weeks time. CONCLUSION: Imatinib mesylate is a drug with curative potential and can be used as a first line drug in the management of CML, however at present the cure rate is unknown.

Lack of degradation of sevoflurane by a new carbon dioxide absorbent in humans.

BACKGROUND: Potent inhaled anesthetics degrade in the presence of the strong bases (sodium hydroxide or potassium hydroxide) in carbon dioxide (CO2) absorbents. A new absorbent, Amsorb (Armstrong Medical Ltd., Coleraine, Northern Ireland), does not employ these strong bases. This study compared the scavenging efficacy and compound A production of two commercially available absorbents (soda lime and barium hydroxide lime) with Amsorb in humans undergoing general anesthesia. METHODS: Four healthy volunteers were anesthetized on different days with desflurane, sevoflurane, enflurane, and isoflurane. End-tidal carbon dioxide (ETCO2) and anesthetic concentrations were measured with infrared spectroscopy; blood pressure and arterial blood gases were obtained from a radial artery catheter. Each anesthetic exposure lasted 3 h, during which the three fresh (normally hydrated) CO2 absorbents were used for a period of 1 h each. Anesthesia was administered with a fresh gas flow rate of 2 l/min of air:oxygen (50:50). Tidal volume was 10 ml/kg; respiratory rate was 8 breaths/min. Arterial blood gases were obtained at baseline and after each hour. Inspired concentrations of compound A were measured after 15, 30, and 60 min of anesthetic administration for each CO2 absorbent. RESULTS: Arterial blood gases and ETCO2 were not different among three CO2 absorbents. During sevoflurane, compound A formed with barium hydroxide lime and soda lime, but not with Amsorb. CONCLUSIONS: This new CO2 absorbent effectively scavenged CO2 and was not associated with compound A production.

High concentrations of isoflurane do not block the sympathetic nervous system activation from desflurane.

PURPOSE: The volatile anesthetic desflurane has been associated with neurocirculatory responses that have been relatively refractory to adjuvant treatment. We have employed desflurane to evaluate the integrity of the sympathetic nerve recording after establishment of the anesthetized state with another anesthetic agent. This retrospective evaluation of data from volunteers determined if higher concentrations of isoflurane that were sufficient to block the neurocirculatory response to laryngeal and tracheal stimulation would abolish the neurocirculatory response to desflurane. METHODS: Data from eight, healthy, young volunteers met our criteria for inclusion. They had been anesthetized with propofol or thiopental and intubated after neuromuscular blockade. Each subject was monitored with radial artery blood pressure (BP), heart rate (HR)(ECG), and sympathetic microneurography. Isoflurane had been administered to achieve a steady state concentration of 1.5 MAC (minimum alveolar concentration) while oxygenation and carbon dioxide were monitored with pulse oximetry and infrared spectrometry, respectively. A deep level of anesthesia was confirmed when laryngoscopy and endotracheal tube movement failed to elicit a neurocirculatory response. A brief exposure to 11% desflurane in the inspired gas was then provided. RESULTS: The responses to desflurane included significant increases in HR, range 32-84 b/min, and BP, range 15-72 mm Hg (P < 0.05). Sympathetic nerve activity increased substantially in the three volunteers with functional nerve recordings. CONCLUSION: In healthy volunteers receiving 1.5 MAC isoflurane, which was sufficient to block the neurocirculatory response to laryngoscopy and tracheal stimulation, there were striking increases in sympathetic outflow, HR and BP when 11% desflurane was substituted for isoflurane.

Absence of bronchodilation during desflurane anesthesia: a comparison to sevoflurane and thiopental.

BACKGROUND: Bronchospasm is a potential complication in anyone undergoing general anesthesia. Because volatile anesthetics relax bronchial smooth muscle, the effects of two newer volatile anesthetics, desflurane and sevoflurane, on respiratory resistance were evaluated. The authors hypothesized that desflurane would have greater bronchodilating effects because of its ability to increase sympathetic nervous system activity. METHODS: Informed consent was obtained from patients undergoing elective surgery with general anesthesia. We recorded airway flow and pressure after thiopental induction and tracheal intubation (baseline) and for 10 min after beginning volatile anesthesia ( approximately 1 minimum alveolar concentration inspired). Respiratory system resistance was determined using the isovolume technique. RESULTS: Fifty subjects were randomized to receive sevoflurane (n = 20), desflurane (n = 20), or thiopental infusion (n = 10, 0.25 mg. kg-1. h-1). There were no differences between groups for age, height, weight, smoking history, and American Society of Anesthesiologists physical class. On average, sevoflurane reduced respiratory resistance 15% below baseline, whereas both desflurane (+5%) and thiopental (+10%) did not decrease respiratory resistance. The respiratory resistance changes did not differ in patients with and without a history of smoking during sevoflurane or thiopental. In contrast, administration of desflurane to smokers resulted in the greatest increase in respiratory resistance. CONCLUSIONS: Sevoflurane causes moderate bronchodilation that is not observed with desflurane or sodium thiopental. The bronchoconstriction produced by desflurane was primarily noted in patients who currently smoked. (Key words: Bronchospasm; respiratory resistance; volatile anesthetics.)

Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions.

This research determined the safety and efficacy of two small-dose infusions of dexmedetomidine by evaluating sedation, analgesia, cognition, and cardiorespiratory function. Seven healthy young volunteers provided informed consent and participated on three occasions with random assignment to drug or placebo. Heart rate, blood pressure, respiratory rate, ETCO(2), O(2) saturation, and processed electroencephalogram (bispectral analysis) were monitored. Baseline hemodynamic measurements were acquired, and psychometric tests were performed (visual analog scale for sedation; observer's assessment of alertness/sedation scale; digit symbol substitution test; and memory). The pain from a 1-min cold pressor test was quantified with a visual analog scale. After a 10-min initial dose of saline or 6 microg. kg(-1). h(-1) dexmedetomidine, volunteers received 50-min IV infusions of saline, or 0.2 or 0.6 microg. kg(-1). h(-1) dexmedetomidine. Measurements were repeated at the end of infusion and during recovery. The two dexmedetomidine infusions resulted in similar and significant sedation (30%-60%), impairment of memory (approximately 50%), and psychomotor performance (28%-41%). Hemodynamics, oxygen saturation, ETCO(2), and respiratory rate were well preserved throughout the infusion and recovery periods. Pain to the cold pressor test was reduced by 30% during dexmedetomidine infusion. Small-dose dexmedetomidine provided sedation, analgesia, and memory and cognitive impairment. These properties might prove useful in a postoperative or intensive care unit setting. IMPLICATIPNS: The alpha(2) agonist, dexmedetomidine, has sedation and analgesic properties. This study quantified these effects, as well as cardiorespiratory, memory and psychomotor effects, in healthy volunteers. Dexmedetomidine infusions resulted in reversible sedation, mild analgesia, and memory impairment without cardiorespiratory compromise.

Renal responses to low-flow desflurane, sevoflurane, and propofol in patients.

BACKGROUND: The contributing factors that result in significant, postoperative proteinuria and glucosuria after low-flow isoflurane and sevoflurane anesthesia are unknown. The present study compared renal responses after anesthesia with desflurane (negligible metabolism), sevoflurane, or intravenous propofol. METHODS: Informed consent was obtained from 52 patients with American Society of Anesthesiologists physical status I-III (aged 36-81 yr). Patients with diabetes or renal insufficiency were excluded. Desflurane (n = 20) or sevoflurane (n = 22), without nitrous oxide, was given at 1 l/min fresh gas flow for elective surgical procedures lasting more than 2 h; 10 patients received propofol without nitrous oxide as the primary anesthetic. Blood and urine chemistries were obtained before surgery. Blood and 24-h urine collections were obtained for 3 days after surgery and were analyzed for liver and renal indices. RESULTS: Length of surgery averaged approximately 300 min (range, 136-750 min), minimum alveolar concentration-hour averaged 4.3 (range, 1.2-11.0), and infusion rates of propofol were 99-168 microg x kg(-1) x min(-1). Plasma creatinine concentration did not change, plasma blood urea nitrogen decreased significantly, and significant increases in urine glucose, protein, and albumin occurred similarly in all groups. Mean (+/- SD) postoperative urine glucose values for day 1 after desflurane, sevoflurane, and propofol were 1.4 +/- 3.0, 1.1 +/- 2.1, and 1.9 +/- 2.6 g/d (normal, < 0.5 g/d). The average daily protein/creatinine ratios for postoperative days 2-3 after desflurane, sevoflurane, and propofol were 240 +/- 187, 272 +/- 234, and 344 +/- 243 (normal, < 150 mg/g). Regardless of anesthetic, there were significantly greater urine protein concentrations after surgical procedures in central versus peripheral regions. CONCLUSIONS: Alterations in postoperative renal function were common and unrelated to the choice of anesthetic. These findings implicate nonanesthetic factors in producing changes in biochemical indices of renal excretory function.

Traditional Chinese medicine for the treatment of dermatologic disorders.

Traditional Chinese medicine (TCM) is an alternative method of therapy that can be administered in oral, topical, or injectable forms. It emphasizes the importance of using many herbs that are combined in different formulations for each individual patient. Among some segments of the patient population, it has become increasingly popular as a mode for treating dermatologic diseases. As a result, it is now worthwhile for dermatologists throughout the West to gain some familiarity with this method. Yet, dermatologists are largely unfamiliar with TCM and may possess some misconceptions. We attempt to give a general overview of TCM through the discussion of different clinical studies involving various TCMs. Some proposed mechanisms of action of TCM are also presented. A discussion of adverse effects, including hepatotoxic effects and the need for close monitoring is discussed. A warning regarding the possible contamination of TCMs is also included. Since it is not possible to discuss the application of TCM for every skin disorder, psoriasis and atopic dermatitis are used as the prototype in illustrating the use of TCM. In the future, perhaps a better understanding of TCM will be gained through more systematic analysis and controlled studies with a placebo arm. It is our hope that this article will provide an overview of the efficacy, mechanism of action, as well as adverse effects of TCM.

Exercise testing with myocardial perfusion imaging in patients with normal baseline electrocardiograms: cost savings with a stepwise diagnostic strategy.

BACKGROUND: It has been suggested that in patients with a normal resting electrocardiogram (ECG), exercise radionuclide myocardial perfusion imaging (MPI) does not add significant incremental diagnostic information to exercise ECG. METHODS AND RESULTS: Of 840 consecutive patients referred for physical exercise MPI, 313 (37%) had normal resting ECGs. There were 189 men and 124 women with a mean age of 54+/-11.9 years. Exercise MPI was performed with either TI-201 or 99mTc-labeled sestamibi. Overall concordance between exercise ECG result and MPI result was 79% (kappa agreement = .54). One hundred eighty-four patients had normal exercise ECG; 181 (98.4%) of these also had normal exercise MPI. In 271 patients with low (< or =20%) to intermediate (21% to 70%) pre-exercise likelihood of coronary artery disease (CAD), concordance between normal exercise ECG and normal MPI was 100%. In the high likelihood (> or =71%) group 3 (15 %) patients with normal exercise ECG had abnormal exercise MPI. Of 129 patients with abnormal exercise ECG, 67 (52%) patients also had abnormal MPI, but 62 (48%) patients had normal MPI. Complete follow-up was obtained in 89% of patients at 9 months. Only 1 hard cardiac event occurred: nonfatal myocardial infarction. Twenty-one (8%) patients had subsequent coronary revascularization or admission with unstable angina. Although both abnormal stress ECG and abnormal exercise MPI were significantly (P < .0001) associated with hard and "soft" events, the association of abnormal exercise MPI was significantly stronger. Because all patients with a low and intermediate likelihood of CAD who had normal exercise ECG also had normal exercise MPI, we propose a stepwise diagnostic testing strategy whereby exercise MPI imaging is performed only in patients with a low to intermediate likelihood of CAD when the exercise ECG is abnormal. When the exercise ECG is performed first, and exercise MPI is performed only when the exercise ECG is abnormal, substantial (38%) cost savings can be achieved. In patients with a high likelihood of CAD, the exercise ECG may be falsely negative, and exercise MPI is preferred. CONCLUSION: In patients with normal resting ECGs a stepwise diagnostic strategy can reduce costs of exercise testing without compromising diagnostic yield when pretest likelihood of coronary artery disease is taken into consideration.