Biomedical subjects
A M Kaiser
Publications and source records attributed to A M Kaiser.
Noninvasive comprehensive characterization of renal artery stenosis by combination of STAR angiography and EPISTAR perfusion imaging.
In a small fraction of patients with hypertension, the cause is stenosis of the renal artery. To date, there is no established noninvasive screening technique available to identify this population, for whom treatment with a surgical procedure or percutaneous transluminal angioplasty is often possible. In this study, the sensitivity and specificity of STAR angiography and EPISTAR perfusion imaging in characterizing renal artery stenosis were evaluated in an animal model. Qualitatively, STAR provided projection angiograms that were comparably sensitive to x-ray angiograms but obtained noninvasively. The sensitivity for detecting the stenosis was 100%. The specificity varied according to the definition of the threshold for significance, which varied 78-94%, depending on whether > 70% or > 50% diameter reduction was considered. Improvements in specificity will depend upon use of shorter echo times and higher spatial resolution. Our preliminary data indicate that EPISTAR provides sensitivity and specificity of 100% for characterizing stenosis with diameter reductions of > 70%.
Acute pancreatitis and contrast medium.
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Apoptotic versus necrotic cell death in acute pancreatitis.
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Effects of cycloheximide on pancreatic endonuclease activity, apoptosis, and severity of acute pancreatitis.
The factors that determine the severity of acute pancreatitis are unknown, but a close inverse correlation between that severity and the extent of acinar cell apoptosis that follows the triggering signal has been previously noted [A. M. Kaiser, A. K. Saluja, A. Sengupta, M. Saluja, and M. L. Steer. Am. J. Physiol. 269 (Cell Physiol. 38): C1295-C1304, 1995]. In the present studies, we have evaluated internucleosomal DNA fragmentation and apoptosis within the pancreas and the effects of inhibiting protein synthesis by cycloheximide (CHX) on these phenomena as well as on the severity of pancreatitis. We report the constitutive presence of a Ca(2+)- and Mg(2+)-dependent endonuclease activity within pancreatic nuclei that is dependent on continued protein synthesis. Furthermore, we have found that CHX administration reduces the extent of apoptosis but significantly worsens the severity of pancreatitis that follows ligation of the rat common bile-pancreatic duct. These observations are consistent with the hypothesis that apoptosis is a teleologically beneficial response to acinar cell injury during acute pancreatitis.
Intravenous contrast medium does not increase the severity of acute necrotizing pancreatitis in the opossum.
Contrast-enhanced computed tomography provides diagnostic and prognostic information in patients with acute pancreatitis. To evaluate whether contrast medium may worsen the severity of acute pancreatitis, we have used a model of necrotizing pancreatitis induced by ligating the common bile-pancreatic duct in opossums. Animals were infused with either saline or an ionic contrast agent 48 and 96 hr after induction of pancreatitis. Hyperamylasemia, pancreatic edema, acinar cell fragility, and macroscopic evidence of pancreatitis were comparable in both experimental groups. The microscopic extent of inflammation was similar in both groups, whereas acinar cell injury/necrosis was less in the contrast group. We conclude that administration of this ionic contrast agent during early stages of necrotizing pancreatitis in the opossum does not worsen the disease severity. The concept that administration of contrast medium during early stages of pancreatitis is dangerous should not be accepted until additional experimental and clinical studies support its validity.
Relationship between severity, necrosis, and apoptosis in five models of experimental acute pancreatitis.
In an effort to elucidate factors that determine the severity of an attack of acute pancreatitis, we have quantitated the extent of necrosis and of apoptosis in five different models of experimental acute pancreatitis. Severe pancreatitis was induced by obstructing the opossum common bile-pancreatic duct, by administering to mice 12 hourly injections of a supramaximally stimulating dose of caerulein, and by feeding young female mice a choline-deficient, ethionine-supplemented diet. In each of these models of severe pancreatitis, marked necrosis but very little apoptosis was found. Mild pancreatitis was induced by obstructing the rat common bile-pancreatic duct and by infusing rats with a supramaximally stimulating dose of caerulein. In contrast to our findings in severe pancreatitis, mild pancreatitis was characterized by very little necrosis but a high degree of apoptosis. Our finding that the severity of acute pancreatitis is inversely related to the degree of apoptosis suggests that apoptosis may be a teleologically beneficial response to acinar cell injury in general and especially in acute pancreatitis.
Evaluation of necrotizing pancreatitis in the opossum by dynamic contrast-enhanced computed tomography: correlation between radiographic and morphologic changes.
BACKGROUND: The ability to quantitate the extent of acinar cell necrosis with contrast-enhanced computed tomography (CT) during acute pancreatitis is uncertain. STUDY DESIGN: Acute hemorrhagic necrotizing pancreatitis was induced in opossums by obstructing their biliopancreatic duct for up to seven days or by retrograde injection of a bile-trypsin taurocholate mixture into the opossum pancreatic duct. At selected times, groups of three animals each were examined by dynamic contrast-enhanced CT, and the abnormalities on the images were quantitated. Immediately following CT, the animals were sacrificed and the extent of necrosis was quantitated by morphometric analysis of tissue samples at the light microscope level. RESULTS: The CT severity score as well as the degree of nonenhancement on dynamic contrast-enhanced CT were both closely correlated with the extent of acinar cell necrosis (r = 0.91 and r = 0.97, respectively). CONCLUSIONS: The degree of pancreatic nonenhancement on dynamic contrast-enhanced CT can be used to quantitate the extent of pancreatic necrosis during acute necrotizing pancreatitis.
Warm chain for breastfeeding.
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Spontaneous abrupt changes in the distribution of ventilation: a cause for apparent mismatching on ventilation/perfusion scintigraphy.
A defect seen in the perfusion scan in a region of lung that is normally ventilated is usually interpreted as indicating pulmonary vascular disease. Since the distribution of 99Tcm macro-aggregated albumin (MAA) represents the distribution of perfusion (Q) only at the time of MAA injection, the assumption is required that the distribution of ventilation (V) remains unchanged between MAA injection and the commencement of imaging. We report the V/Q scintigraphic findings in six patients (including four children), in whom this assumption could not be sustained. Thus ventilation imaged with 81Krm was seen to change during image acquisition in lobes that showed perfusion abnormalities. In some, but not all, views the appearances were typical for pulmonary vascular disease, which might easily have been misdiagnosed if the changes in the distribution of ventilation had not announced themselves by occurring during image acquisition. A ventilation image obtained immediately before injection of 99Tcm-MAA may be useful.
Outcome of infants shunted for post-haemorrhagic ventricular dilatation.
Between April 1980 and March 1986, 19 infants underwent cerebrospinal fluid (CSF) shunting procedures for post-haemorrhagic ventricular dilatation at the Hammersmith Hospital, London. A total of 58 shunt-related procedures have been performed on these children. The major perioperative complication was seizure activity (eight children). Postoperative complications included infection (12 shunts) and blockage (29 shunts). Prophylactic antibiotics failed to prevent shunt infection. The likelihood of the first shunt failing was significantly reduced by greater weight of the infant and lower CSF protein at surgery. Long-term outcome was poor: three have died and another four are quadriplegic with severe mental retardation. Only four children are developmentally normal. These outcomes cannot be related to the shunt surgery or its complications, but correlate best with pre-operative parenchymal brain-lesions, as shown on ultrasound scans.
Hypertensive response to raised intracranial pressure in infancy.
Mean arterial pressure and intracranial pressure were measured serially in six infants with intracranial hypertension (intracranial pressure greater than 20 mm Hg), and cerebral perfusion pressure was calculated from their difference. Overall, mean arterial pressure increased with rising intracranial pressure at a mean rate of 0.20 mm Hg/mm Hg. This caused a fall in cerebral perfusion pressure with increasing intracranial pressure at a mean rate of 0.80 mm Hg/mm Hg overall, although cerebral perfusion pressure was well maintained in one infant. Thus the rise in blood pressure was usually insufficient to compensate for the increase in intracranial pressure. In infants with acute encephalopathy vigorous blood pressure support is as important as lowering intracranial pressure.
Non-invasive monitoring of intracranial pressure--fact or fancy?
Ladd and Wright fontanelle pressure meters were applied to the heads of 18 babies, and simultaneously the intracranial pressure was monitored directly. Increasing the force with which the meters were applied caused a linear increase in registered fontanelle pressure. No universally optimal application force could be determined. To obviate this, application force was increased until the fontanelle pressure was calibrated with directly measured intracranial pressure. Subsequent variations in intracranial pressure were significantly correlated to fontanelle pressure, but not closely enough for clinical reliability. The correlation was similar if the meter was affixed instead directly to the scalp with collodion gel, and the clinical reliability improved. Applanation fontanometers are strongly affected by variations in the method by which they are applied and may not be a reliable reflection of intracranial pressure. If directly affixed to the scalp, however, they may yield clinically useful data.
Intracranial pressure estimation by palpation of the anterior fontanelle.
Simultaneous assessment of intracranial pressure by anterior fontanelle palpation and direct measurement from a cerebrospinal fluid cannula showed that mean pressure was significantly different between 'soft' (5.4 mm Hg) and 'tense' (14.0 mm Hg) fontanelles, but with considerable overlap. Normal fontanelle tone was often confirmed, whereas clinical assessment of raised intracranial pressure was unreliable.
Normal cerebrospinal fluid pressure in the newborn.
Lumbar CSF pressure (CSFP) was measured on 61 occasions, in 49 babies undergoing lumbar puncture as part of a septic screen, by means of Gaeltec pressure transducers. In normal circumstances, intracranial pressure (ICP) has the same value. Measurements were made when the baby was horizontal and quiet, with the head deflexed. For acceptance of the measurement, it was essential for the CSF to be clear and to show pressure pulses with respiration, heartbeat and jugular occlusion. The mean CSFP and standard deviation were 2.8 +/- 1.4 mm Hg (3.8 +/- 1.9 cm water), with a normal range of 0 to 5.7 mm Hg (0 to 7.6 cm water). This value is similar to previous reports of CSFP measured invasively in infants, but is much lower than the "ICP" established noninvasively. No relationship was found between birthweight, gestational age, current weight, postmenstrual age, or postnatal age and CSFP.
Cerebrospinal fluid pressure during post haemorrhagic ventricular dilatation in newborn infants.
Post haemorrhagic ventricular dilatation occurs in a minority of newborn infants, but is associated with a high risk of cerebral palsy and developmental delay. Neither the relation of ventricular size to cerebrospinal fluid (CSF) pressure, nor the effect of CSF removal on prognosis, have been established. Normal CSF pressure measured at subarachnoid cannulation was mean (SD) 2.8 (1.4) mm Hg. Values were significantly higher in post haemorrhagic ventricular dilatation--9.1 (3.7) mm Hg when the ventricles were expanding, and 4.5 (2.4) mm Hg when they were static or contracting. No significant relation between head circumference and CSF pressure was found in this series. Raised CSF pressure is associated with progressive ventricular dilatation, and may contribute to the increased risk of neurological abnormality.
Measurement of metabolism in multiple organ failure.
Despite the emphasis on surgical nutrition, clinical research and practice are usually based on gross estimation of caloric requirements and no specific knowledge of caloric balance. One reason for this is the difficulty of measuring O2 and CO2 exchange in critically ill patients. We designed a system for intensive care unit (ICU) bedside measurement of O2 consumption (VO2), CO2 production (VCO2), respiratory quotient (RQ), and indirect calorimetry (E). We measured these variables daily in 57 surgical ICU patients at risk for multiple organ failure. Measured VO2 and E varied widely (+/- 40%) from estimated values. Seventeen patients had a cumulative negative balance of at least 10,000 calories; 13 died. This caloric deficient was reversed by caloric intake in three of these patients; one died. Fifteen patients had positive caloric balance. Only four of these died, but the CO2 load produced by hypercaloric feeding created ventilator weaning problems in some patients. Ventilator weaning was facilitated by decreasing total calories and substituting fat for carbohydrate to reduce the RQ. The incidence of multiple organ failure was higher in patients with large caloric deficits, although cause and effect are not inferred. We conclude that respirometry and indirect calorimetry are helpful for management and essential for nutritional research.