Absence of physiological tolerance to cocaine in pregnant sheep.

OBJECTIVE: To determine whether repetitive administration of cocaine to sheep during pregnancy altered basal hemodynamic states in the mother and fetus, and to determine whether this cocaine exposure would alter subsequent hemodynamic responses to cocaine. METHODS: Cocaine or saline was administered to 16 pregnant sheep daily from day 75 to day 128 of gestation (term = 145 days). At 128 days' gestation, maternal and fetal basal physiological measurements, including organ-specific blood flow in the fetus, were determined. Each experimental and control ewe then received cocaine 2 mg/kg and these physiological parameters were again measured over the next 30 min to determine whether the experimental animals had developed tolerance to the effects of cocaine. RESULTS: No differences were seen in basal physiological parameters between treatment groups. Likewise, following an acute administration of cocaine, physiological parameters in both groups responded in a similar fashion. Fetal hypoxemia occurred in both groups after the ewe received cocaine. In response to hypoxemia, whether it was the animals' first or 53rd exposure to cocaine, fetal cerebral, myocardial and adrenal blood flow increased so that oxygen delivery was unimpaired. CONCLUSIONS: For the cardiovascular parameters measured in this study, we found no tolerance to cocaine in the ewe or fetus. The acute hemodynamic effects of maternal cocaine administration were as severe for animals having received it more than 50 times as for those that received it for the first time.

Clofazimine-induced crystal-storing histiocytosis producing chronic abdominal pain in a leprosy patient.

Clofazimine-induced crystal-storing histiocytosis is a rare but well-recognized condition in the literature. Besides the common reddish discoloration of the skin, clofazimine produces gastrointestinal disturbances-sometimes severe abdominal pain, prompting exploratory laparotomy, because pathologic and radiologic findings can produce diagnostic difficulties if the pathologic changes caused by clofazimine are not recognized. The authors report such a case in a leprosy patient to emphasize the importance of history taking, the radiologic abnormalities of the small intestine, and the pathologic findings in small intestine and lymph node biopsies. Clofazimine crystals are red in the frozen section and exhibit bright-red birefringence. However, they are clear in routinely processed histologic sections because they dissolve in alcohol and organic solvents. They also appear as clear crystal spaces during electron microscopic study, but some osmiophilic bodies can be observed. Histiocytosis caused by clofazimine crystals produces infiltrative lesions in radiologic studies mimicking malignant lymphoma or other infiltrative disorders. Associated plasmacytosis in the histologic sections can simulate lymphoplasmacytic lymphoma or multiple myeloma with crystal-storing histiocytosis. With the knowledge of this rare condition caused by clofazimine, appropriate management to avoid an unnecessary laparotomy is possible.

The potential role of intraoperative ultrasonography in the surgical treatment of hilar cholangiocarcinoma.

The role of intraoperative ultrasonography (IOU) in the surgical treatment of hilar cholangiocarcinoma was explored in twenty-two patients, 17 males and 5 females. The mean age was 55 years (range 36-78 years). Preoperative imaging studies included abdominal ultra-sonography and/or CT scan, and visceral angiography. Operations performed were segment III bypass in 18 patients, local resection of tumour in 2 and resection of tumour en bloc with left hepatectomy in 2. Interpretation of IOU in terms of vascular involvement by the tumour (as compared to angiography or operative findings) was correct in 21 patients; no vascular invasion in 20 and portal vein invasion in the remainder. One false negative result occurred in a patient whose IOU failed to show right hepatic artery encasement by the tumour. When compared to postoperative cholangiography or surgical specimen, IOU correctly demonstrated location and extent of the tumours in all but one patient who had incomplete tumour resection. IOU was also helpful in locating segment III duct for biliary bypass. The mean time used for IOU was 15.1 min (range 10-20 min.), and there was no procedure-related complication. When supplemented with operative exploration, IOU seems to be very useful in the assessment of the resectability of hilar cholangiocarcinoma.

Metabolic acidemia with hypoxia attenuates the hemodynamic responses to epinephrine during resuscitation in lambs.

OBJECTIVE: To examine the effects of metabolic acidemia and hypoxia on the hemodynamic responses to epinephrine in an intact neonatal animal model. DESIGN: Multi-experiment, randomized, controlled trial. SETTING: Animal research laboratory of a university hospital. SUBJECTS: Sixteen lambs, ranging in age from 2 to 14 days. INTERVENTIONS: The lambs were chronically catheterized; the ductus arteriosus was ligated; and a pulmonary arterial flow probe was inserted to measure cardiac output, blood pressure (BP), and heart rate. In the first protocol, hemodynamic responses to epinephrine during pure metabolic acidemia or metabolic alkalosis were studied in eight lambs. Each lamb was studied on four different days at a different arterial pH: 6.9, 7.1, 7.4, and 7.6. Ventilation was controlled to maintain PCO2 at 35 to 45 torr (4.66 to 5.99 kPa). Acidemia was induced by the infusion of lactic acid and alkalosis by the infusion of sodium bicarbonate. When the appropriate arterial pH was achieved, 10 micrograms/kg of epinephrine was administered intravenously. In a second protocol, hemodynamic responses to epinephrine during metabolic acidemia or alkalosis plus hypoxia were studied in eight lambs. When the appropriate arterial pH was achieved, hypoxia was induced until cardiac output decreased to 40% of baseline. Epinephrine bolus was given, and after 90 secs, the lambs were resuscitated with oxygen. MEASUREMENTS AND MAIN RESULTS: Epinephrine administered during uncompromised hemodynamics led to hypertension, bradycardia, and decreased cardiac output that were unaffected by arterial pH values between 6.9 and 7.6. Acidemia with hypoxia compromised hemodynamics with decreases in heart rate and cardiac output. Epinephrine administered during this compromised condition did not improve cardiac output, heart rate, or BP before resuscitation with oxygen at any arterial pH studied. Resuscitation with epinephrine and oxygen during hemodynamically compromised states led to increases in heart rate, BP, and cardiac output with significant attenuation of these hemodynamic responses during metabolic acidemia at pH values of 6.9 and 7.1. CONCLUSIONS: During the physiologic conditions associated with neonatal resuscitation, that is, hypoxia with a compromised hemodynamic state, metabolic acidemia significantly attenuates the hemodynamic responses to resuscitation with epinephrine and oxygen. Correction of metabolic acidosis may be warranted in newborn resuscitation.