Pegylated interferon and ribavirin is the “gold-standard” of treatment for chronic hepatitis C. We report a case of acute hearing loss during treatment with pegylated interferon and ribavirin. Only one other reported case describes this association.1 A 54 yo white male dentist underwent treatment for chronic hepatitis C (genotype 2B, viral load: 1,000,000 copies/ml, histology: grade 2 stage 1). Pegylated interferon and ribavirin decreased viral load and normalized transam-inases without significant effect on hematologic parameters. At treatment week 14, the patient noted acute hearing loss. An MRI was normal. Pure tone audiogram showed 50% sensorineural hearing loss in the right ear and diminished discrimination. Conduction was normal. Upon evaluation of the patient's past medical history, family history and medications, it was thought that the hearing loss was secondary to pegylated interferon. Antiviral therapy was discontinued and a prednisone taper was prescribed. At two weeks, hearing was restored. Due to the profound nature of the hearing loss, potential for permanent deficit and presence of mild histologic injury re-treatment with interferon was not instituted. Sudden hearing loss has been associated with standard interferon therapy.2,3 A recent report describes hearing loss associated with pegylated- interferon.1 Proposed etiologies for auditory dysfunction associated with interferons include direct ototoxicity with high dose interferon, hematological changes4, autoimmune-mediated microvascular damage5, and idiopathic. During treatment with pegylated interferon and ribavirin, patients should be routinely questioned about hearing loss. If symptoms arise, auditory function should be closely monitored and therapy may need to be discontinued.

Background: An initial multicenter study using a 21 mm flanged esophageal Z stent demonstrated excellent palliation but an 11% immediate complication rate at placement and a 27% migration rate at 1 month. This North American multicenter trial prospectively studied a 25 mm flanged Z stent to define its palliative ability and whether the increased diameter affected placement or migration problems. Methods: Fifty patients who had esophageal Z stents at seven university or regional referral hospitals were prospectively studied. Indications for prosthesis placement, previous therapy, patient demographics, incidence of concomitant tracheoesophageal fistula, and degree of dysphagia were defined, as were procedural and subsequent stent-related problems, survival times, the ability to occlude a tracheoesophageal fistula, and subsequent degree of dysphagia. Results: Twenty-four patients had infiltrating malignancy (16 exophytic and 10 extrinsic), 9 of whom had concomitant tracheoesophageal fistulas. Ten patients (20%) had misplaced stents requiring retrieval and replacement, 12 patients (24%) had subsequent stent-related problems including exsanguination (2), aspiration (3), tumor overgrowth (3), and postplacement migration (4) (8%). There was statistically significant improvement in prestent versus poststent dysphagia and two thirds of patients had complete occlusion of their tracheoesophageal fistula. Conclusions: Redesign of the esophageal Z stent has decreased the migration rate without increasing placement or subsequent erosion problems. Its efficacy appears comparable to the currently marketed Z stent for the palliation of malignant dysphagia and occlusion of tracheoesophageal fistula. (Gastrointest Endosc 1997;46:156-60.)

Most studies testing vasoactive agents in portal-hypertensive rats have been performed in young animals. To assess age-related changes in hemodynamic responses to adrenergic stimuli, we examined (a) responsiveness to norepinephrine (0.14 to 12.0 micrograms.kg-1.min-1) in young (3-mo-old) and aged (9-mo-old) sham-operated and portal-hypertensive rats and (b) response to propranolol (2 and 10 mg.kg-1 body wt), nitroglycerin (3.6 mg.kg-1.min-1) or saline solution in aged portal-hypertensive rats. Aged rats exhibited significantly (p < 0.05) smaller responses to norepinephrine with regard to increases in mean arterial pressure and superior mesenteric arterial vascular resistance, irrespective of portal hypertension. Portal hypertension alone potentiated this reduced response in aged animals and was associated with cardiovascular hyporesponsiveness to norepinephrine in young rats. Portal pressure was significantly (p < 0.05) lower in aged sham-operated rats than in young sham-operated rats over a wide range of norepinephrine doses. Portal-hypertensive aged rats showed significantly (p < 0.05) lower heart rates. Furthermore, systemic and splanchnic cardiovascular responses to propranolol and nitroglycerin mediated by the sympathetic nervous system were decreased or negligible in aged rats, compromising the portal-hypotensive effects of these drugs. In summary, aged rats express diminished cardiovascular responsiveness to adrenergic stimuli. Therefore age should be considered an important factor in studies evaluating pharmacological agents for the treatment of portal hypertension.

To exclude possible confounding effects of anesthesia on splanchnic hemodynamics, two different awake postanesthetic models (PAM), restrained and unrestrained, have been used. However critical analysis of the splanchnic hemodynamic state in these models is not available. We conducted experiments using chronically implanted pulsed-Doppler flow probes on the superior mesenteric artery (SMA) in ketamine-anesthetized and in postanesthetic restrained and unrestrained normal rats. Baseline values of mean SMA flow were compared with those under anesthesia (30 min), PAM (restrained or unrestrained at 90 and 150 min), and reanesthesia. Sham-anesthetized unrestrained animals provided control values. The same animals (n = 7) underwent the restrained, unrestrained, and control experiments at least 5 days apart. Ketamine anesthesia did not significantly alter mean SMA flow (89 +/- 9% of baseline) compared with sham-anesthetized controls (99 +/- 9%). Mean SMA flow in both PAM, restrained and unrestrained, had a significant (P < 0.05) decrease at 90 min (78 +/- 8 and 83 +/- 12%) and at 150 min (68 +/- 14 and 78 +/- 14%) when compared with baseline and control. Reanesthesia returned SMA flows to baseline values (91 +/- 16%). The variability of mean SMA flow was significantly increased in both PAM. Maximum variability was observed in the restrained model (69 +/- 32%). These results indicate 1) that ketamine anesthesia does not significantly alter SMA flow and 2) that both the restrained and unrestrained PAM exhibit significant alterations of the splanchnic circulation for at least 2 h after complete recovery from anesthesia. Thus, in the absence of critical evaluation, results of splanchnic hemodynamic studies with these models should be questioned. Ketamine anesthesia administered intra-muscularly may be preferred to the awake PAM for the study of the splanchnic circulation.

Portal hypertension is accompanied by hyperdynamic systemic and splanchnic circulation. Serum bile acids (BAs), which are elevated in portal hypertension and have vasodilatory properties, have been proposed as mediators of this hyperdynamic circulation. In this study, portal hypertensive rats [accomplished by partial portal vein ligation (PVL)] were gavaged with cholestyramine (PVL-CH) to decrease circulating BA levels. A control group of rats was gavaged with an inert suspension of Metamucil (PVL-ME). The following hyperdynamic parameters were found to be similar in PVL-CH and PVL-ME: mean arterial pressure (119 +/- 6 vs. 124 +/- 5 mmHg), portal pressure (13.2 +/- 0.6 vs. 14.5 +/- 0.5 mmHg), cardiac index (0.33 +/- 0.04 vs. 0.34 +/- 0.03 ml.min-1.g body wt-1), splanchnic blood flow (1.4 +/- 0.13 vs. 1.6 +/- 0.1 ml.min-1.g body wt-1), portosystemic shunting (82 +/- 8 vs. 92 +/- 3%), peripheral arteriolar resistances (344 +/- 74 vs. 387 +/- 29 mmHg.min.ml-1.g body wt), and splanchnic arteriolar resistances (75 +/- 14 vs. 72 +/- 6 mmHg.min.ml-1.g splanchnic wt; 1,471 +/- 150 vs. 1,325 +/- 120 mmHg.min.ml-1.g body wt). BA in PVL-ME (84 +/- 9 microM/l) were similar to those previously observed in untreated PVL and significantly greater than those measured in PVL-CH (25 +/- 4 microM/l; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Expansion of plasma volume may be necessary for the development of the hyperdynamic circulation in portal hypertension. In experiment 1, sham portal vein-constricted (sham PVL) rats were divided into normal diet (NL diet sham) and low-sodium diet (low-Na sham) groups. Data obtained from the NL diet sham group was used as control data in studying portal hypertensive rats, which were also divided into normal diet (NL diet PVL) and sodium-restricted (low-Na PVL) groups on the day of portal vein constriction. There were no hemodynamic differences at 3 wk between sham PVL rats on the two diets. In contrast, sodium restriction in PVL rats resulted in a significant amelioration of the hyperdynamic circulation. In experiment 2, PVL rats were fed a normal diet for 10 days, followed by allocation to NL diet PVL and low-Na PVL groups. The hemodynamic effects of sodium restriction in these animals (studied at 22 and 28 days after PVL) were similar to those observed in experiment 1. A time course for amelioration of the hyperdynamic circulation in PVL rats by sodium restriction is described. Sodium restriction prevents the expansion of the plasma volume in PVL rats. Interference with plasma volume expansion blunts the development of (and can ameliorate) the hyperdynamic syndrome. Plasma volume expansion seems necessary for the development of the hyperdynamic circulation in portal hypertension.

Systemic hemodynamic effects of portal hypertension in arterial hypertension and their relationship to serum bile acid levels were investigated using spontaneously hypertensive rats 2 and 15 weeks after partial portal vein ligation (SHR-PVL) or sham operation (SHR-SH) and normotensive controls. Mean arterial pressure in SHR-PVL at 2 weeks was decreased to normal due to a decrease in peripheral resistance. Mean arterial pressure and peripheral resistance in SHR-PVL at 15 weeks did not differ from SHR-SH. Resolution of this arterial hypotensive effect and systemic hyperdynamic circulation was associated with decreased portal-systemic shunting. Bile acid levels were increased in both SHR-PVL groups. These results suggest that an endogenous circulating vasodilator(s) associated with portal hypertension ameliorates the systemic vasoconstriction in SHR. Bile acids, while not direct mediators of these hemodynamic events, may be prototypic of this vasodilator. This arterial hypertensive model may aid further investigation of the mechanisms contributing to the hyperdynamic state in portal hypertension.

Biloma has been defined as an extraductular collection of bile within a defined capsular space. Prior reports have documented an association of biloma with abdominal trauma and abdominal surgery. Biloma has not been reported in association with or as the presenting manifestation of hepatocellular carcinoma. In addition, hepatocellular carcinoma has not been previously reported in an HIV-seropositive patient. We present the case of an HIV-seropositive patient with hepatocellular carcinoma complicated by a biloma.

A new small noninvasive pressure-sensitive capsule for the endoscopic measurement of esophageal varix pressure was evaluated and compared to an initial Yale-designed capsule to test the hypothesis that the diameter of the capsule measuring surface is a limiting factor for the accuracy and variability of capsule pressure measurements. Capsule pressures obtained with each capsule, using rabbit mesenteric vessels comparable in size to human esophageal varices, were correlated with direct intraluminal pressure measurements. There was an excellent correlation between capsule pressure measurements obtained with the small capsule and intraluminal pressure (r2=0.97)which was significantly greater than the correlation obtained when the initial capsule was studied (r2=0.89, P<0.01). The variability of capsule pressure measurements obtained with the small capsule was less than that observed when measurements were obtained with the initial capsule (P<0.01).Therefore, this new small capsule should provide the most accurate and reproducible noninvasive measurements of variceal pressure.