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Because of its nonpungent odor and low blood-gas solubility coefficient, sevoflurane might be an ideal drug for single-breath inhaled induction of anesthesia. Fifty ASA grade I-III ambulatory surgical patients (18-76 yr old) received a single-breath induction with either 5.0% sevoflurane or 5.0% isoflurane (randomized) in a 1:1 N2O/O2 mixture. Anesthesia was maintained with the same anesthetic in 70% N2O until the end of surgery, when anesthetics were abruptly discontinued. Induction times (loss of eyelash reflex) were similar for sevoflurane (75 +/- 3 s, mean +/- se) and isoflurane (67 +/- 4 s, P = not significant). Sevoflurane patients were less likely to have complications during induction (P < 0.005); coughing occurred more frequently with isoflurane (P < 0.001). During induction, heart rate increased with both sevoflurane (from 73 +/- 3 to 90 +/- 4 bpm, P < 0.05) and isoflurane (from 70 +/- 2 to 92 +/- 2 bpm, P < 0.05); the increase with isoflurane was greater than that with sevoflurane. Times to eye opening for sevoflurane (8.1 1 +/- 1.0 min) did not differ significantly from those for isoflurane (10.6 +/- 1.3 min). Patients opened their eyes at lower end-tidal minimum alveolar anesthetic concentration (MAC)-fractions of sevoflurane (0.12 +/- 0.01 MAC) than isoflurane (0.15 +/- 0.01 MAC, P < 0.01). During recovery, patients who received sevoflurane felt less clumsy (P < 0.001) and less confused (P < 0.005) but had higher pain scores (P < 0.005) than those who received isoflurane. Sevoflurane is more suitable than isoflurane for single-breath induction, because it produces a smoother induction with a lower incidence of complications and better patient acceptance.

Background/aims: There is limited information on treatment options for massive, highly symptomatic polycystic liver disease. The aim of the study was to analyze the immediate and long-term outcome of combined liver resection and fenestration., Methods: Information was abstracted from medical records. Follow-up was obtained by mailed questionnaire. Liver volume was quantified by computed tomography., Results: Thirty-one patients underwent liver resection and fenestration between July 1985 and June 1993. Mean liver volume was 9357 mL before and 3567 mL after surgery. There was one death from postoperative intracerebral bleed. Eighteen patients experienced complications, usually transient pleural effusions or transient ascites. Twenty-eight of 29 surviving patients with adequate follow-up have experienced immediate and sustained relief of symptoms and improvement in quality of life. After median follow-up of 2.4 years (range, 0.2 to 7.9 years), most patients have not had clinically significant enlargement of the liver. Sequential computed tomography scans before and after surgery suggest that hepatic enlargement in the age range of the patients in the study mainly resulted from the expansion of existing cysts rather than from the development of new cysts., Conclusions: Selected patients with severe symptomatic polycystic liver disease and favorable anatomy benefit from liver resection and fenestration with acceptable morbidity and mortality. The extent of hepatic resection and fenestration is important for the long-term effectiveness of this procedure.

To discuss the clinical presentation, diagnosis, and treatment of hepatic venous outflow obstruction as a complication of polycystic liver disease, four cases diagnosed and treated at our institution have been reviewed and the information from six previously published case reports has been summarized. Eight of the 10 patients were women. All presented with severe ascites. Nine had polycystic kidneys. Three had moderate-to-advanced renal insufficiency, four were on hemodialysis, and one had a renal allograft. Possible predisposing factors were identified in seven patients; the most common was recent abdominal surgery, which, in three cases, was a bilateral nephrectomy. All patients had extrinsic compression of the hepatic veins and the inferior vena cava by hepatic cysts, and four had proven superimposed thrombosis of the inferior vena cava and/or hepatic veins. In the patients seen in this institution, magnetic resonance imaging was helpful in determining the level of obstruction in the inferior vena cava and the patency of the hepatic and portal veins. The outcome was worse in the patients with thrombosis; one recovered after a portocaval shunt, and the remaining three patients died. On the other hand, five of the six patients without thrombosis recovered after alcohol sclerosis of a large dominant cyst (one patient) or after hepatic resection and cyst fenestration (four patients). Hepatic venous outflow obstruction probably has been underrecognized as a cause of portal hypertension, ascites, and liver dysfunction in polycystic liver disease. The diagnosis can be reliably established with current imaging techniques, especially magnetic resonance imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Although diphenhydramine is frequently used to treat pruritus and nausea in patients who have received neuraxial opioids, there are no data regarding its effect on ventilatory control. We conducted the current study to evaluate the effects of diphenhydramine on hypercapnic and hypoxic ventilatory control in healthy volunteers., Methods: First, we measured the steady-state ventilatory response to carbon dioxide during hyperoxia with an end-tidal carbon dioxide tension of 46 or 54 mmHg (alternate subjects) in eight healthy volunteers. We then determined the hypoxic ventilatory response during isocapnic rebreathing at the same carbon dioxide tension. After a 10-min recovery period, we repeated the steady-state and hypoxic ventilatory response measurements at the other carbon dioxide tension (54 or 46 mmHg). Ten minutes after subjects received diphenhydramine 0.7 mg.kg-1 intravenously, we repeated this sequence of ventilatory measurements., Results: Under hyperoxic conditions (inspired oxygen fraction > 0.5) diphenhydramine did not affect the ventilatory response to hypercapnia. Similarly, at an end-tidal carbon dioxide tension of 46 mmHg, neither the slope nor the position of the hypoxic ventilatory response curve changed significantly after diphenhydramine. However, at an end-tidal carbon dioxide tension of 54 mmHg, the slope of the hypoxic ventilatory response increased from 1.28 +/- 0.33 to 2.13 +/- 0.61 l.min-1.%SpO2(-1) (mean +/- standard error), and VE at an arterial hemoglobin oxygen saturation of 90% increased from 31.2 +/- 3.1 to 43.1 +/- 5.4 l.min-1)., Conclusions: We conclude that although it did not affect the ventilatory response to carbon dioxide during hyperoxia or the ventilatory response to hypoxia at an end-tidal carbon dioxide tension of 46 mmHg diphenhydramine augmented the hypoxic response under conditions of hypercapnia in our young healthy volunteers. Although these findings may help to explain the apparent safety of diphenhydramine, they may not be applicable to debilitated patients or those who have received systemic or neuraxial ventilatory depressants.

Background: Propofol infusion at subanesthetic doses provides reliable conscious sedation. However, the ventilatory effects of sedative doses of propofol have not been established. The current study was conducted to determine the effects of propofol sedation on the hypoxic ventilatory response., Methods: Eight healthy, male volunteers received 1 mg.kg-1 propofol followed by a propofol infusion adjusted to maintain a constant, subanesthetic level of sedation. Hypoxic ventilatory response was measured using an isocapnic rebreathing technique: while keeping PETCO2 constant (approximately 6 mmHg above prestudy baseline), the authors continuously recorded minute ventilation and tidal volume, as oxygen saturation (SpO2) decreased from 98 to 70%. Hypoxic response determinations were performed before and during propofol infusion, as well as 30 and 60 min after termination of the propofol infusion., Results: The slope of the hypoxic ventilatory response curve (VE vs. SpO2) decreased from 0.88 +/- 0.15 to 0.17 +/- 0.03 l.min-1.%SpO2 -1 during propofol sedation (mean +/- SE). Thirty minutes after discontinuation of the propofol infusion, slope returned to its prepropofol value. In addition, minute ventilation at SpO2 = 90% decreased during propofol sedation, from 16.1 +/- 0.8 to 8.7 +/- 0.4 l.min-1, accompanied by a similar decrease in tidal volume at SpO2 = 90%, from 1,099 +/- 87 to 523 +/- 21 ml. Thirty minutes after discontinuation of the propofol infusion, these variables also returned to their prepropofol values., Conclusions: The authors concluded that propofol infusion for conscious sedation significantly decreases the slope and causes a downward shift of the hypoxic ventilatory response curve measured during isohypercapnia.

The prevalence of spontaneous bacterial peritonitis (SBP) or its variants, bacterascites (BA), and culture-negative neutrocytic ascites (CNNA), may vary depending on the underlying liver disease and protein content of ascites. In this study, we compared the frequency of peritonitis (SBP, BA, CNNA) upon admission in alcoholic (ALD), cholestatic (CLD), and hepatocellular liver disease (HLD); determined the relationship between Child's class and prevalence of peritonitis; and assessed ascitic total protein as a risk factor for peritonitis. Between January 1989 and April 1991, 113 consecutive patients were admitted with chronic liver disease and ascites (49, ALD; 22, CLD; and 42, HLD). All had admission paracentesis. SBP was defined as polymorphonuclear cell count (PMN) > or = 250 mm3 with a positive culture, BA as PMN < 250/mm3 and positive culture, and CNNA as PMN > or = 250/mm3 with negative culture. No patients with obvious intraabdominal source for infection (i.e., secondary peritonitis) were included in the analysis. The prevalence of peritonitis was 8/113 (7%); four patients had SBP, one BA, and three CNNA. The occurrence of peritonitis was independent of the type of liver disease (ALD, 8%; CLD, 9%; HDL, 5%). Neither ascitic fluid total protein nor the severity of liver disease (Child's class) predicted the occurrence of peritonitis. We conclude that the occurrence of peritonitis is unrelated to the type of liver disease, and severity of liver disease did not predict the presence of peritonitis. Also, ascitic fluid total protein < 1.0 g/dl may not be a sensitive predictor of risk of peritonitis.

To determine whether needle polarity significantly affects nerve stimulation during peripheral nerve block, we performed a randomized double-blinded study of 10 patients undergoing axillary block for upper extremity surgery. Using an insulated needle, we determined the minimum current necessary to elicit muscle contraction with positive and negative needle polarity at two needle placements: (A) where stimulation was first observed and (B) where stimulation was maximal. At Position A, stimulation required significantly more current when the needle was positive (2.32 +/- 0.45 mA, mean +/- SEM) than when it was negative (1.05 +/- 0.23 mA, P < 0.001). Similarly, at Position B, stimulation required more current when the needle was positive (1.49 +/- 0.49 mA) than when it was negative (0.47 +/- 0.15 mA, P < 0.001). The mean ratio of positive to negative threshold stimulation current at Position B (3.11 +/- 0.20) was significantly greater than that at Position A (2.37 +/- 0.19, P < 0.05). Our results emphasize the importance of attaching the negative terminal of the nerve stimulator to the stimulating electrode. Use of the positive terminal could lead to abandoning a block if stimulation were not obtained at a low enough current; alternatively, motor contraction might not be observed before neural contact or vascular puncture.

We report high-volume postobstructive choleresis in two patients who underwent transhepatic external drainage for malignant biliary obstruction. Excessive loss of bicarbonate-rich biliary fluid (up to 6.5 L/day) caused orthostatic hypotension, prerenal insufficiency, hyponatremia, and a decrease in serum bicarbonate. Therapy with isotonic fluids containing sodium, chloride, lactate, bicarbonate, and potassium was based on measurement of biliary fluid volume and electrolyte concentrations. Biliary fluid loss was terminated by conversion to internal biliary drainage. The reason for this rare complication of external drainage of biliary obstruction is unknown, but such patients must be closely monitored for volume loss. When high-volume choleresis occurs, biliary fluid and electrolyte losses should be precisely measured and replaced, and external biliary drainage converted to internal drainage.

The effects of sedative infusions of propofol on the processed electroencephalograms (EEG) of eight healthy male volunteers were studied. EEG data for aperiodic analysis were collected during three 5-min periods: before propofol, during propofol infusion, and 30 min after termination of the infusion. After an initial dose of 1 mg/kg, subjects received a propofol infusion titrated to produce a standard level of conscious sedation. The infusion rate was 84 +/- 27 micrograms.kg-1 x min-1 (mean +/- SE) and plasma propofol levels were 2180 +/- 43 ng/mL. Total EEG power, defined as the sum of the squares of peak-to-peak amplitudes during each 5-s epoch, increased from 1350 +/- 295 microV2 x epoch-1 to 9675 +/- 2390 microV2 x epoch-1 during the propofol infusion (P < 0.05); it returned to 1445 +/- 145 microV2 x epoch-1 30 min after the infusion was discontinued (P < 0.05 vs the result during propofol). The change in total power was accompanied by a change in the distribution of power within the EEG spectrum, as the fraction of activity in the beta-band (12-35 Hz) increased during the infusion from 23% +/- 3% to 44% +/- 5% (P < 0.05). Thirty minutes after the infusion was terminated, the distribution of activity within the EEG spectrum had reverted to pre-propofol patterns. The similarity of EEG effects seen with sedative doses of propofol and benzodiazepines suggests that these drugs may share some neurochemical effects.

We enrolled 32 patients with chronic hepatitis C into a randomized, controlled trial to evaluate the efficacy of recombinant alpha-2a-interferon treatment. Sixteen patients were randomized to receive 1.5 million units of recombinant alpha-2a-interferon subcutaneously, thrice weekly, for six months while the remaining 16 patients were randomized to a control group that received no treatment. The mean serum alanine aminotransferase (ALT) level during the six-month study period, expressed as a percentage of the prestudy baseline value, was 82% for the control group compared to 56% for the treatment group (P = 0.014). One fourth of the treatment group normalized their serum ALT level compared to only 6% of the controls (P = 0.05). During posttherapy follow-up, 86% of responders clinically relapsed. Loss of anti-HCV IgM and HCV RNA occurred exclusively in interferon-treated responders. Anti-interferon antibodies developed in 32% of all treated patients. Forty percent of nonresponders developed anti-interferon antibodies compared to only 14% of responders (P = NS). We conclude that recombinant alpha-2a-interferon is clinically effective in patients with chronic hepatitis C. However, most responders in this trial of low-dose interferon relapsed upon cessation of treatment.

Background: While flumazenil reverses benzodiazepine-induced sedation, its ability to antagonize the ventilatory depressant effects of benzodiazepines has not been fully established. A randomized, double-blind study was conducted to determine whether flumazenil effectively reverses midazolam-induced depression of the hypoxic ventilatory response., Methods: Twelve healthy male volunteers received intravenous midazolam 0.12 +/- 0.01 mg.kg-1 followed by either flumazenil 1.0 mg or placebo. Hypoxic ventilatory response was measured using an isocapnic rebreathing technique: as Spo2 decreased to 70% VE and tidal volume were continuously recorded. Hypoxic response determinations were performed before and after midazolam, as well as 3, 30, 60, 120, and 180 min after flumazenil or placebo., Results: After midazolam, the slope of the hypoxic ventilatory response curve (VE vs. SpO2) decreased to 0.59 +/- 0.05 (means +/- SE) times its premidazolam baseline; likewise, at Spo2 = 90%, minute ventilation (VE90) and tidal volume (TV90) decreased to 0.70 +/- 0.04 and 0.62 +/- 0.03 times baseline, respectively. Three minutes after flumazenil, the slope increased to 1.10 +/- 0.13 times baseline (P < 0.05 vs. postmidazolam), while following placebo, it was only 0.81 +/- 0.09 times baseline (P = NS vs. postmidazolam, P < 0.05 between treatments). VE90 and TV90, after flumazenil, increased to 1.45 +/- 0.15 and 1.27 +/- 0.09 times baseline, respectively (P < 0.05 vs. postmidazolam); these increases were significantly greater than the corresponding changes observed after placebo (P < 0.05 between treatments)., Conclusions: It was concluded that, after sedation with midazolam, flumazenil causes a greater increase in hypoxic ventilatory response during isohypercarbic conditions than does placebo, and may, therefore, be useful in the treatment of midazolam-induced ventilatory depression.

Increased intracranial pressure is present in more than 80% of patients with fulminant hepatic failure. However, patients with encephalopathy secondary to chronic liver disease are thought not to develop elevated intracranial pressure. We report two patients with chronic liver disease in hepatic coma with raised intracranial pressure documented by an epidural intracranial pressure monitor. One patient rapidly deteriorated to coma over a period of 4 h. The other patient progressively worsened following intravenous sedation administered during upper endoscopy. Both patients had generalized tonic-clonic seizures, and one demonstrated decerebrate posturing and papilledema. Although all metabolic and structural abnormalities should be excluded in patients with hepatic encephalopathy, if the etiology remains in question, the possibility of increased intracranial pressure should be considered in patients with chronic liver disease.

To determine whether the risk of midazolam-induced ventilatory depression is related to the rate of midazolam administration, we compared the effect of rapid (over 15 s) and slow (over 5 min) administration of midazolam (0.1 mg/kg IV) on the hypercarbic ventilatory response of 10 healthy volunteers. During the first 5 min after the start of midazolam injection, the slope of the ventilatory response to CO2 was significantly lower when the subjects received midazolam rapidly (P less than 0.001). However, after completion of the infusion (between 5 and 20 min), depression of the CO2 response curve slope was independent of the rate of midazolam administration. Similarly, although minute ventilation and tidal volume measured at an end-tidal CO2 tension of approximately 46 mm Hg decreased more quickly after rapid administration of midazolam (P less than 0.001), these variables did not differ significantly between the two rates of administration once the slow infusion was complete. These results suggest that slow administration of midazolam provides no independent protection from respiratory depression.

To improve our understanding of the respiratory pharmacology of intravenous induction agents, the authors compared the acute effects of intravenous (iv) propofol 2.5 mg.kg-1 and iv thiopental 4.0 mg.kg-1 on the ventilatory response to CO2 (VeRCO2) of eight healthy volunteers. The slope of VeRCO2 decreased from 1.75 +/- 0.23 to a minimum of 0.77 +/- 0.14 1.min-1.mmHg-1 (mean +/- standard error) 90 s after propofol; similarly, the slope of VeRCO2 decreased from 1.79 +/- 0.22 to a minimum of 0.78 +/- 0.23 l.min-1.mmHg-1 30 s after thiopental. For both drugs, the slope was less than control in the 0.5-5-min period after injection (P less than 0.05). The slope returned to baseline within 6 min after thiopental; in contrast, after propofol, the slope remained less than control for the entire 20-min follow-up period (P less than 0.05 at 6-10, 11-15, and 16-20 min after injection). Also, from 6-10, 11-15, and 16-20 min after injection, the slope was less after propofol than at corresponding times after thiopental (P less than 0.05). Recovery of consciousness was approximately 4 min slower after propofol than after thiopental; nonetheless, awareness scores returned to baseline within 14 min after both drugs. The authors conclude that propofol 2.5 mg.kg-1 iv produces longer-lasting depression of VeRCO2 than a 4.0 mg.kg-1 iv dose of thiopental; after propofol, ventilatory depression may persist despite apparently complete recovery of consciousness.

The unexpected diagnosis of herpetic esophagitis in a patient with nausea led us to review our experience with this disease. Review of our records from 1979 to 1989 produced 23 cases proven by endoscopic culture or microscopic examination (Cowdry-type A inclusions), the largest such series reported to date. Twenty-two of the 23 patients were immunocompromised. Odynophagia and chest pain were each present in half of the cases, but 26% of patients had neither. Gastrointestinal bleeding was attributable to herpetic esophagitis in 30%. Thirty percent of patients had disseminated herpes simplex infection and 70% had simultaneous infections with other organisms. Endoscopic findings included nonspecific inflammation, discrete ulcers, coalescent ulcers, and pseudomembranous esophagitis. Herpes virus was not suspected endoscopically as the cause of esophagitis in 30% of cases. Culture was slightly more sensitive than microscopic examination for diagnosis (89% vs. 76%), but both methods should be employed in any immunocompromised patient with esophagitis.

The authors compared the analgesic efficacy of one dose of oral ibuprofen with that of intravenously administered fentanyl for relief of pain after outpatient laparoscopic surgery. Thirty healthy female patients received either 800 mg of oral ibuprofen preoperatively or 75 micrograms of intravenous fentanyl intraoperatively plus respective intravenous or oral placebos in a randomized, double-blind manner. Patients recorded their degree of pain and nausea in the recovery room, in the same-day surgery stepdown unit, during the ride home, and upon arrival at home. The postanesthesia care nurse recorded the amount of fentanyl and droperidol needed to treat pain and nausea in the recovery room. Patients who received ibuprofen were more comfortable in the stepdown unit (P less than 0.05) and after arrival home (P less than 0.05) than those in the fentanyl group. Additionally, patients who received ibuprofen had lower nausea scores in the step-down unit (P less than 0.05); this may have been related to the lower total fentanyl dose in these patients. The authors conclude that ibuprofen may be a useful alternative to fentanyl for providing postoperative analgesia for outpatient surgery.

Flumazenil, a benzodiazepine antagonist, reliably reverses midazolam-induced sedation; however, its effect on respiratory depression has not been established completely. Twelve healthy volunteers received sufficient midazolam (0.13 +/- 0.01 mg.kg-1 mean +/- SE) to render them unresponsive to verbal command; they then received flumazenil 1.0 mg or placebo (flumazenil vehicle) in a randomized, double-blind fashion. Ventilatory drive was measured before and after administration of midazolam, as well as 3, 30, 60, and 120 min after administration of flumazenil or placebo. Seven to 30 days later, the study was repeated, with subjects receiving placebo or flumazenil (whichever they had not received during their first trial). Midazolam caused significant decreases in the slope of the CO2 response (-29 +/- 5%; P less than 0.005); minute ventilation (VE) at end-tidal CO2 tension (PETCO2) = 46 mmHg (-28 +/- 4%; P less than 0.001), and tidal volume at PETCO2 = 46 mmHg (-44 +/- 4%; P less than 0.005). Three minutes after intravenous administration of flumazenil 1.0 mg, VE46 and tidal volume increased to 108 +/- 6% and 105 +/- 6%, respectively, of their premidazolam values; at the same time after administration of placebo, VE46 and tidal volume remained significantly depressed (between groups, P less than 0.005 for each variable). Thirty minutes later, these variables did not differ between groups, probably because the effects of flumazenil and midazolam were diminishing.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors conducted a randomized, prospective study comparing epidural morphine with patient-controlled intravenous (iv) morphine in 30 patients recovering from total hip or total knee arthroplasty. Six, 18, and 24 hr postoperatively, patients used a 10 cm visual-analogue scale to indicate both their current degree of discomfort and the maximum discomfort they had experienced since the previous evaluation. Pain at the time of evaluation did not differ between patients receiving epidural (2.6 +/- 0.4 cm, mean +/- SEM) and patient-controlled iv morphine (3.4 +/- 0.3 cm). However, patients who received epidural morphine recalled less pain during the period preceding evaluation (4.2 +/- 0.5 cm) than did those receiving patient-controlled analgesia (5.5 +/- 0.4 cm, P less than 0.05). Patients receiving epidural morphine were more likely to require treatment for pruritus (4 of 15) than patients who received patient-controlled iv morphine (none of 15, P less than 0.05). Minimum respiratory rates were lower in patients receiving epidural morphine (15.0 +/- 0.3) than in those receiving patient-controlled analgesia (16.5 +/- 0.4, P less than 0.05), but no patients required treatment for respiratory depression. The authors conclude that epidural morphine may provide more consistent analgesia following joint replacement surgery than patient-controlled morphine; however, there is a higher incidence of side-effects with the epidural technique.

The authors performed a clinical trial in 313 patients in labor to determine the safety and efficacy of an air test for unintentional intravenous placement of epidural catheters. Following routine aspiration for blood and cerebrospinal fluid, 1 ml of air was injected through each epidural catheter while heart tones were continually monitored with a Doppler ultrasound probe placed over the maternal precordium. In 281 patients, Doppler heart tones did not change following air injection (negative air test). All but eight of these patients developed an adequate level of analgesia following anesthetic administration, and no patients with negative air tests developed signs or symptoms of local anesthetic toxicity (false-negative rate, 0%; 95% confidence limits, 0.0-1.1%). Doppler heart tone changes followed air injection in 22 cases (positive air test). In 16 of these, intravenous catheter position was subsequently shown by aspiration of blood from the catheter or by the use of test doses consisting of local anesthetics with or without epinephrine. In six cases, adequate levels of analgesia developed despite a positive air test (false-positive rate, 2%; 95% confidence limit, 0.7-4.3%). None of the 303 patients receiving the air test developed any complications attributable to the injection of air (95% confidence limits, 0.0-1.0%). The authors conclude that air, with precordial Doppler detection, is a safe and effective test for identifying intravenously located epidural catheters.

To characterize the syndrome of hepatic cyst infection in autosomal dominant polycystic kidney disease (ADPKD) and to review its diagnosis and management, we retrospectively studied five such cases in patients from our institution and nine detailed case reports from the literature. The clinical manifestations were an acute (58%) or subacute (42%) febrile illness, typically associated with tenderness in the right upper quadrant, leukocytosis, a very high erythrocyte sedimentation rate, but minor abnormalities of liver function tests. Bacteremia was present in 7 of 11 patients. Enterobacteriaceae grew in pure culture from the cyst fluid in 9 of 12 patients. Complex cysts were observed by ultrasonography (in four of eight patients), computed tomography (in six of nine), and magnetic resonance imaging (in two of two). 111In leukocyte scans were positive in all four patients in whom they were done, and 67Ga scans were positive in only one of three patients. An unfavorable outcome was observed in six of seven patients treated with only antibiotics, in contrast with one of seven patients who received antibiotics and early drainage. In two patients, ciprofloxacin cyst levels were 2.3 and 4.8 times higher than the level in serum; in a third patient, cyst levels remained in therapeutic range 30 hours after the last dose of ciprofloxacin, at which time serum levels were undetectable. Clinical and laboratory features and the use of modern scanning techniques facilitate a prompt diagnosis of infection in hepatic cysts in ADPKD. The treatment of choice is a combination of percutaneous drainage and antimicrobial therapy.

A biopsy study of 60 allografts from 53 patients after orthotopic liver transplantation (OLT) revealed prominent centrilobular necrosis (CN) in 18% of the grafts that were suitable for analysis. The lesions often had a "punched-out" appearance, sometimes with unusual features such as giant cell formation. Persistent CN developed 4 weeks to 6 months after OLT, and persisted in two cases for 2 years and longer. In some instances, CN disappeared or healed by scarring. We found no association between CN and rejection arteritis or arteriopathy. Ductopenic (chronic) rejection subsequently occurred in six of eight livers with CN. Overall, patients with persistent CN had a worse prognosis than control patients. A comparison of cases with matched controls failed to reveal significant differences with respect to perioperative factors such as ischemia time, immunologic test results such as lymphocyte crossmatches, drug administration--in particular, of azathioprine, frequency of cellular (acute) rejection or infection episodes, or frequency of complications affecting major hepatic vessels or bile ducts. Morphologic evidence suggests that in some instances, rejection-induced endotheliitis/phlebitis of hepatic vein branches may lead to sinusoidal outflow blockage, sinusoidal dilatation, and dropout of hepatic cell plates. Although potentially reversible conditions such as ischemia or adverse drug reactions are among the possible causes of CN, severe rejection leading to ductopenia appears to be the most important underlying condition. Thus, presence of CN in repeated biopsy specimens from allografts should be considered a warning sign of irreversible rejection.

A randomized study was carried out to determine whether the administration of oxygen (3 liter/min) via nasal prongs significantly affects arterial oxygenation during colonoscopy in patients sedated with intravenous midazolam (2.6 +/- 0.2 mg, means +/- SE) and meperidine (48 +/- 3 mg). Patients who received supplemental oxygen were less likely to become hypoxic (pulse oximeter reading, SpO2 less than 90%) than those who breathed room air (10 of 28 vs. 22 of 28, p less than 0.005). Similarly, the total time during which SpO2 was below 90% was significantly less in patients receiving nasal oxygen (0.7 +/- 0.3 min) than in patients breathing room air (9.7 +/- 1.9 min, p less than 0.001). Minimum oxygen saturations were significantly higher in patients receiving oxygen (90.6 +/- 0.8%) than in patients breathing air (86.5 +/- 0.8%, p less than 0.001). In patients breathing air, there was a significant negative correlation between the dose of meperidine and the minimum observed oxygen saturation; conversely, midazolam dose did not correlate with indices of hypoxemia. The authors conclude that administration of oxygen via nasal prongs can reduce the risk of hypoxemia during colonoscopy. However, since hypoxemia may occur even when nasal oxygen is given, continuous monitoring of arterial oxygenation is recommended.

Using a dual-isohypercapnic technique, the authors determined the effect of equipotent doses of methohexital (1.5 mg/kg) and etomidate (0.3 mg/kg) on the ventilatory response to CO2 (VERCO2) in six healthy volunteers. Speed of induction and duration of hypnosis did not differ significantly between the two drugs. Within 2 min after injection, the slope of VERCO2 decreased significantly after both methohexital (from 2.52 to a minimum of 0.15 l . min-1 . mmHg-1, P less than 0.05) and etomidate (from 2.56 to a minimum of 0.62 l . min-1 . mmHg-1, P less than 0.05); the magnitude of this depression did not differ significantly between the drugs. Methohexital also caused a significant decrease in minute ventilation at end-tidal PCO2 of 46 mmHg (VE 46) from 14.6 to 4.3 l . min-1 within 60 s after injection (P less than 0.05). In contrast, after etomidate VE 46 gradually increased from 17.9 1 . min-1 to a maximum of 31.6 l . min-1 at 3.5 min after injection (P less than 0.05); respiratory rate increased significantly, while changes in tidal volume were not significant. Effects of etomidate and methohexital on VE 46 differed significantly (P less than 0.001). These data indicate that, while etomidate and methohexital similarly depress the medullary centers that modify ventilatory drive in response to changing CO2 tensions, ventilation at any given CO2 tension is greater after etomidate than after methohexital. This indicates that etomidate may cause a CO2-independent stimulation of ventilation, suggesting its use for induction of anesthesia in cases where maintenance of spontaneous ventilation is desirable.

A young man and his father, both with pancreatitis, were recently seen at the Mayo Clinic. The histories, physical findings, and laboratory values were those of chronic pancreatitis. Endoscopic retrograde cholangiopancreatography was valuable in confirming the gross pathological changes and in orienting the surgeon preoperatively.

The analgesic and ventilatory depressant effects of epidural and intramuscular alfentanil (15 micrograms/kg) were compared in two groups of seven healthy unpremedicated subjects. Fifteen minutes after IM injection, the slope of the ventilatory response to CO2 decreased significantly (from 2.72 +/- 0.34 to 1.8 +/- 0.20 L.min-1.mmHg-1) while assessment of periosteal analgesia showed no change. After epidural injection, the slope of the ventilatory response to CO2 decreased significantly (from 2.32 +/- 0.42 to 1.61 +/- 0.29, 1.51 +/- 0.29, and 1.53 +/- 0.21 L.min-1.mm Hg-1) at 15, 45, and 90 minutes (x +/- SD, P less than 0.05), and there was significant periosteal analgesia of the tibia (15 and 30 minutes after injection) and of the radius (30 to 90 minutes after injection). Throughout the study, plasma alfentanil levels were similar after intramuscular and epidural injection. These results suggest that epidural alfentanil induces ventilatory depression due to the rostral spread of the drug rather than to systemic absorption.

The authors studied the effect of changes in arterial carbon dioxide tension on plasma lidocaine concentrations during a constant lidocaine infusion in eight healthy volunteers. With a PaCO2 of 41.4 +/- 0.9 mmHg (mean +/- SE), total plasma lidocaine concentrations were 3.97 +/- 0.20 microgram X ml-1. There was no significant change associated with hypercarbia (PaCO2 = 55.7 +/- 1.5 mmHg, lidocaine = 3.93 +/- 0.18 microgram X ml-1) or hypocarbia (PaCO2 = 19.5 +/- 1.4 mmHg, lidocaine = 4.29 +/- 0.25 microgram X ml-1), despite the known effects of changes in CO2 tension on hepatic blood flow and lidocaine protein binding. During hypercarbia, plasma lidocaine binding decreases while total plasma lidocaine remains essentially constant; therefore, increased CO2 tensions could cause toxicity if total lidocaine concentrations were in the high therapeutic range (5 micrograms X ml-1). Four subjects experienced transient symptoms of mild lidocaine toxicity during acute increases in carbon dioxide tension.

The authors determined the accuracy of the Ohmeda 3700 (version J) pulse oximeter in healthy volunteers rendered hypoxic (SaO2 from 60-98%) by breathing mixtures of O2 in N2. When equipped with an ear probe, the pulse oximeter reading (y) reliably predicted arterial saturation (x) under steady-state conditions (y = 1.05x - 4.66, r = 0.98) as well as when oxygen saturation was rapidly decreasing (y = 1.05x - 6.38, r = 0.96). Conversely, when equipped with a finger probe, the oximeter tended to significantly underestimate steady-state arterial saturation (y = 1.21x - 19.1, r = 0.98, P less than 0.001). In response to this information, the manufacturer modified the oximeter's software (version XJ1), resulting in improved agreement between oximeter readings and arterial values (y = 0.96x + 4.59, r = 0.99). Despite the close correlation between steady-state oximeter readings and arterial saturation, the 99% prediction limits for both the ear and finger probes (version XJ1) were +/- 8%. Finger probe readings did not reliably reflect radial arterial oxygenation during rapid desaturation (y = 0.55x + 45.2, r = 0.78). This may be related to the time required to "arterialize" the blood in the finger; during acute resaturation, we found that the ear- to finger-probe delay was 24.0 +/- 2.3 s (means +/- SE, P less than 0.001).

The effects of intravenous ketamine (bolus of 2 mg.kg-1 followed by a continuous infusion at a rate of 40 micrograms.kg-1.min-1) on ventilatory response to carbon dioxide were studied in nine children ranging in age from 6 to 10 yr and in weight from 20 to 48 kg. Ketamine did not affect resting respiratory rate, tidal volume, end-tidal CO2 tension (PETCO2), or minute ventilation. Five minutes after the ketamine bolus, the slope VE/PETCO2 decreased significantly (P less than 0.05) from 1.71 +/- 0.47 to 1.05 +/- 0.23 1.min-1.mmHg-1 (mean +/- SD). After 30 min of continuous iv ketamine infusion, the slope returned to 1.65 +/- 0.44 1.min-1.mmHg-1, a significantly higher value (P less than 0.05) compared with the nadir and not significantly different from control. The minute ventilation at a PETCO2 of 60 mmHg decreased from 824 +/- 98 to 626 +/- 26 ml.kg-1.min-1 5 min after iv ketamine, and remained depressed (640 +/- 125 ml.kg-1.min-1 P less than 0.05) throughout the 30-min ketamine infusion. In addition, the slope VT/PETCO2 and the VT 60 did not change during the study; nonetheless, the slope f/PETCO2 and the f 60 decreased significantly following iv bolus ketamine, and the f 60 remained significantly decreased following ketamine infusion. The authors conclude that clinically useful doses of iv ketamine significantly alter ventilatory control in children.

Using new, specially designed ultrafiltration devices and an enzyme immunoassay technique, the authors determined the effect of carbon dioxide tension on the fractional binding of lidocaine to human plasma proteins. Identical samples of serum at therapeutic (2.2 micrograms X ml-1) and toxic (6.8 micrograms X ml-1) lidocaine concentrations were tonometered at 37 degrees C to CO2 tensions between 0.13 and 10.7 kPa (1.0 to 80.5 mmHg). The fraction of unbound lidocaine increased linearly with increasing pCO2 (r = 0.93, p less than 0.001). These changes help to explain the increased central nervous system toxicity of lidocaine associated with hypercarbia.

We investigated the hypothesis that lysosomes are the main source of biliary copper in conditions of hepatic copper overload. We used a rat model of oral copper loading and studied the relationship between the biliary output of copper and lysosomal hydrolases. Male Sprague-Dawley rats were given tap water with or without 0.125% copper acetate for up to 36 wk. Copper loading produced a 23-fold increase in the hepatic copper concentration and a 30-65% increase in hepatic lysosomal enzyme activity. Acid phosphatase histochemistry showed that copper-loaded livers contained an increased number of hepatocyte lysosomes; increased copper concentration of these organelles was confirmed directly by both x ray microanalysis and tissue fractionation. The copper-loaded rats showed a 16-fold increase in biliary copper output and a 50-300% increase in biliary lysosomal enzyme output. In the basal state, excretory profiles over time were similar for biliary outputs of lysosomal enzymes and copper in the copper-loaded animals but not in controls. After pharmacologic stimulation of lysosomal exocytosis, biliary outputs of copper and lysosomal hydrolases in the copper-loaded animals remained coupled: injection of colchicine or vinblastine produced an acute rise in the biliary output of both lysosomal enzymes and copper to 150-250% of baseline rates. After these same drugs, control animals showed only the expected increase in lysosomal enzyme output without a corresponding increase in copper output. We conclude that the hepatocyte responds to an increased copper load by sequestering excess copper in an increased number of lysosomes that then empty their contents directly into bile. The results provide direct evidence that exocytosis of lysosomal contents into biliary canaliculi is the major mechanism for biliary copper excretion in hepatic copper overload.

The efficacy of two dosage regimens of intravenous naloxone were compared to avoid nonrespiratory side effects and respiratory depression and yet to preserve analgesia (maximum tolerance to periostial pressure over the tibia) after administration of 200 micrograms epidural fentanyl. Three groups of eight patients were studied: group 1 patients received a loading dose of 0.4 mg IV naloxone followed by naloxone infusion at a rate of 10 micrograms.kg-1.hr-1. Group II patients received a loading dose of 0.2 micrograms naloxone followed by a naloxone infusion at a rate of 5 micrograms.kg-1.hr-1. Group III patients received a saline infusion at a rate of 20 ml/hr. Epidural fentanyl significantly increased tolerance to periostial pain in all three groups (respectively, +38 +/- 20%, +36 +/- 16%, and +35 +/- 14%) (mean +/- SD; P less than 0.05). The naloxone infusion significantly reduced this effect in groups I and II, respectively, -40 +/- 20% and -37 +/- 28% below prenaloxone levels) (P less than 0.05). Nonrespiratory side effects were also reversed in groups I and II. In group III, neither periostial analgesia nor nonrespiratory side effects were affected. The baseline slopes of VE/PETCO2 were 2.34 +/- 1.01, 2.14 +/- 0.66, and 2.68 +/- 1.14 L.min-1.mm Hg-1, respectively, in groups I, II, and III. Epidural fentanyl significantly decreased the slope below baseline levels in each group: -21 +/- 16%, -22 +/- 17%, and -19 +/- 32%, respectively, in groups I, II and III.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary sclerosing cholangitis is a chronic, cholestatic syndrome characterized by fibrosing inflammation of the bile ducts that may lead to cirrhosis and death from liver failure. Previous reports have suggested abnormal hepatic copper metabolism in this disease. Therefore, in 70 patients, we prospectively determined the levels of hepatic copper, serum copper, and serum ceruloplasmin, and the rate of urinary copper excretion to assess the diagnostic and prognostic usefulness of these tests. Virtually all patients had at least one abnormal copper test. Hepatic copper levels were elevated in 87% of patients [292 +/- 38 micrograms/g dry wt (mean +/- SE)] and 24-h urinary copper levels in 64% of patients [135 +/- 15 micrograms/24 h (mean +/- SE)] to values comparable to those seen in Wilson's disease or primary biliary cirrhosis. In advanced histologic stages of primary sclerosing cholangitis, progressively higher mean levels of hepatic and urinary copper were found. In the liver, mean copper content (in micrograms per gram dry weight) in disease stages I and II was 147 +/- 36 (mean +/- SE); in stage III (fibrosis), 302 +/- 68; and in stage IV (cirrhosis), 379 +/- 69. In the urine, mean copper excretion (in micrograms per 24 h) in stages I and II was 72 +/- 14 (mean +/- SE); in stage III, 100 +/- 14; and in stage IV, 207 +/- 30. Higher hepatic and urinary copper levels at initial evaluation were associated with decreased survival during a median follow-up period of 2.6 yr: patients with hepatic copper greater than 250 micrograms/g dry wt and urinary copper excretion greater than 200 micrograms/24 h at initial evaluation had an 18-mo survival of less than 60%. We conclude that abnormal copper metabolism is a universal feature of primary sclerosing cholangitis, that hepatic copper accumulates and urinary copper excretion increases as the disease progresses, and that the hepatic copper concentration and the 24-h urinary copper determination are useful prognostic indicators in this disease.

Cortical and outer medullary collecting duct segments were dissected from human kidneys and perfused in vitro. The transepithelial potential difference was measured and found to be lumen positive +6.8 +/- 0.6 mV (n= 20). This lumen-positive potential difference was inhibited by ouabain and furosemide but not by acetazolamide. Replacement of chloride in bath and perfusion fluids caused a reversible decrease of the potential difference to near zero. We conclude from these studies: (a) the lumen-positive potential difference is dependent upon the presence of chloride ion suggesting the existence of an active electrogenic chloride reabsorptive process in the human collecting duct and (b) it is possible to examine human renal physiology directly using in vitro microperfusion of tubule segments.

The authors conducted a double-blind crossover study to determine the effects of physostigmine salicylate on hyperoxic ventilatory response to carbon dioxide (VE RCO2) and on awareness in healthy subjects previously sedated with diazepam. Diazepam 0.4 mg/kg iv decreased the slope of VE RCO2 from 2.41 +/- 0.19 to 1.30 +/- 0.15 1 . min-1 . mmHg-1 (mean +/- SEM, P less than 0.001). Subsequent injection of physostigmine 2.0 mg iv was associated with a 0.20 +/- 0.28 1 . min-1 . mmHg-1 decrease in slope; this was significantly different from the 0.56 +/- 0.22 1 . min-1 . mmHg-1 increase in slope associated with saline placebo (P less than 0.05). Level of consciousness, on the other hand, increased more after physostigmine than after saline (P less than 0.01). The authors conclude that despite an apparent increase in awareness resulting from physostigmine administration, the accompanying decrease in ventilatory drive may contraindicate its use in patients who previously have received diazepam.

The effect of tubular obstruction on renal function has been understood poorly at the tubular level and from the clinical standpoint. In our review the evidence for a direct influence of hydrostatic pressure on tubular transport and glomerular filtration is examined. The data generated to date indicate a direct influence of hydrostatic pressure on tubular transport only at the level of the distal convoluted tubule and collecting duct. With respect to glomerular filtration increased tubular pressure reduces the net driving force for filtration and reduces glomerular filtration rate in the absence of a compensatory increase in glomerular hydrostatic pressure. We next review physiological data concerning the mechanism of post-obstructive diuresis. Available information suggests 4 factors that play a significant role in the clinical syndrome of post-obstructive diuresis: 1) medullo-papillary washout, 2) decreased fractional and absolute salt and water reabsorption in the collecting duct, presumably secondary to direct influence of hydrostatic pressure on transport mechanisms, 3) osmotic diuresis secondary to retention of urea and other osmotic solutes during the period of obstruction and 4) prior salt and water administration in the absence of excretion, resulting in extracellular fluid volume expansion.

Dual isohypercapnic studies on the time course of depression following intravenous diazepam permit detailed analysis of changes in the ventilatory response to carbon dioxide. The mean slope of the CO2 response curves of eight healthy volunteers dropped from 2.38 to 1.21 1 . min-1 . mmHg-1 ( P less than 0.05) within three minutes after injection of diazepam 0.4 mg/kg. Twenty-five minutes after injection, the slope was only 1.49 1 . min-1 . mmHg-1, still significantly lower than control (P less than 0.05). At 30 min, the slope has increased to 1.73 1 . min-1 . mmHg-1 and was no longer different from control at the 0.05 level of significance. There was also a significant correlation between the slope of the CO2 response curve and level of consciousness (r = 0. 81). There was little or no displacement of the response curve at any selected ventilation except as accounted for by the slope change. The authors conclude that ventilatory depression resulting from intravenous diazepam begins within one minute and lasts at least 25 min after injection.