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Biomedical subjects

J Pearl

Publications and source records attributed to J Pearl.

At least 19 recordsLinked to original sources

Comparison of laparoscopic ultrasonography and fluorocholangiography in 300 patients undergoing laparoscopic cholecystectomy.

BACKGROUND: This study compares laparoscopic ultrasonography to fluorocholangiography in detecting common bile duct (CBD) stones and delineating biliary anatomy. METHODS: A prospective nonrandomized study of 300 consecutive patients undergoing laparoscopic cholecystectomy in a university hospital was performed. After port placement but before dissection, laparoscopic ultrasonography of the extrahepatic CBD was performed in both transverse and longitudinal planes. Cystic duct fluorocholangiography was attempted in all patients. RESULTS: Of 300 patients, CBD stones were detected in 26 (9%) with 25 of these (96%) detected on laparoscopic ultrasonography. Sonography identified the location and size of the CBD as well as anomalous anatomy prior to dissection. No CBD injuries were encountered. End-fire transducers were easier to use than rigid or flexible side-fire transducers; all gave excellent image quality. CONCLUSIONS: In this large study, laparoscopic ultrasonography and fluorocholangiography were equally sensitive in detecting CBD stones. Sonography delineates the biliary anatomy noninvasively and does not require dissection or opening of the biliary system. Laparoscopic ultrasonography may improve the safety of laparoscopic cholecystectomy, especially in cases of acute inflammation or distorted anatomy.

Cholangiography

Causal diagrams for epidemiologic research.

Causal diagrams have a long history of informal use and, more recently, have undergone formal development for applications in expert systems and robotics. We provide an introduction to these developments and their use in epidemiologic research. Causal diagrams can provide a starting point for identifying variables that must be measured and controlled to obtain unconfounded effect estimates. They also provide a method for critical evaluation of traditional epidemiologic criteria for confounding. In particular, they reveal certain heretofore unnoticed shortcomings of those criteria when used in considering multiple potential confounders. We show how to modify the traditional criteria to correct those shortcomings.

Epidemiologic Methods

Causal inference from indirect experiments.

An indirect experiment is a study in which randomized control is replaced by randomized encouragement, that is, subjects are encouraged, rather than forced, to receive a given treatment program. The purpose of this paper is to bring to the attention of experimental researchers simple mathematical results that enable us to assess, from indirect experiments, the strength with which causal influences operate among variables of interest. The results reveal that despite the laxity of the encouraging instrument, data from indirect experimentation can yield significant and sometimes accurate information on the impact of a program on the population as a whole, as well as on the particular individuals who participated in the program.

Humans

Prospective evaluation of the safety and efficacy of laparoscopic jejunostomy.

We prospectively assessed the safety and efficacy of laparoscopic jejunostomy done by 11 surgeons in 8 medical centers using the T-fastener technique. In all, 23 men and 13 women aged 19 to 84 (mean, 59) years required enteral feeding, but could not undergo gastrostomy and had no contraindication to laparoscopy. Of these patients, 12 had head and neck cancer and 11 had neurologic swallowing dysfunction. The procedure took 25 to 180 minutes (mean, 75). Three (8%) early cases were converted to open jejunostomy because of accidental enterotomies caused by inappropriate techniques that were avoided in later cases. Minor technical problems, such as passing a needle through the back wall of the jejunum, occurred in 7 patients, but they were easily corrected and produced no complications. Feedings were routinely begun within 24 hours of the surgical procedure. All jejunostomy catheters functioned well. This is a safe and effective technique when done by experienced laparoscopic surgeons, and serious complications are rare.

Adult

Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome.

The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria. The main outcome measure was survival at 30 days after randomization. Survival was not significantly different in the 19 mechanical ventilation (42%) and 21 new therapy (extracorporeal) (33%) patients (p = 0.8). All deaths occurred within 30 days of randomization. Overall patient survival was 38% (15 of 40) and was about four times that expected from historical data (p = 0.0002). Extracorporeal treatment group survival was not significantly different from other published survival rates after extracorporeal CO2 removal. Mechanical ventilation patient group survival was significantly higher than the 12% derived from published data (p = 0.0001). Protocols controlled care 86% of the time. Average PaO2 was 59 mm Hg in both treatment groups. Intensity of care required to maintain arterial oxygenation was similar in both groups (2.6 and 2.6 PEEP changes/day; 4.3 and 5.0 FIO2 changes/day). We conclude that there was no significant difference in survival between the mechanical ventilation and the extracorporeal CO2 removal groups. We do not recommend extracorporeal support as a therapy for ARDS. Extracorporeal support for ARDS should be restricted to controlled clinical trials.

Adult

Ethical implications of standardization of ICU care with computerized protocols.

Ethical issues related to the use of computerized protocols to control mechanical ventilation of patients with Acute Respiratory Distress Syndrome (ARDS) are identical to the ethical issues surrounding the use of any therapy or intervention. Four ethical principles must be considered: nonmaleficence, beneficence, autonomy, and distributed justice. The major ethical challenges to computerized protocol use as a specific application of clinical decision support tools are found within the principles of nonmaleficence and of beneficence. The absence of credible outcome data on which ARDS patient survival probabilities with different therapeutic options could be based is a constraint common to most ICU clinical decision making. Clinicians are thus deprived of the knowledge necessary to define benefit and are limited to beneficent intention in clinical decisions. Computerized protocol controlled decision making for the clinical management of mechanical ventilation for ARDS patients is ethically defensible. It is as well supported as most ICU therapy options.

Clinical Protocols

The 24-hour D/P ratio is a convenient screen for identifying altered peritoneal transport rates.

Peritoneal transport characteristics (PTC) may change without peritonitis, surgery, or other insults. Identifying patients with these changes is essential in adjusting the dialysis prescription to achieve optimal peritoneal dialysis on a long-term basis. Frequent standard peritoneal equilibration tests (PETs) become impractical as the population in individual programs expands. The time demands are burdensome to the nursing staff as well as to the patient. The accuracy of fast PETs is dependent upon the patient's exact adherence to the protocol steps. Utilizing the 24-hour D/P as a marker for altered PTCs has improved the efficiency of our approach to repeating standard PETs and ensuring dialysis adequacy. For adequacy studies, pooled 24-hour dialysate is routinely collected in our unit. The 24-hour D/P ratio correlates well with extrapolations from original PET data and the patient's current dwell times. Discrepancies noted between the patient's actual D/P ratio and the patient's expected D/P ratio alert the clinician to possible PTC changes.

Biological Transport

The microvascular distribution of cardioplegic solution in the piglet heart. Retrograde versus antegrade delivery.

The uniform distribution of cardioplegic solution to all areas of the microvasculature is considered critical for myocardial protection. Despite this, little information exists regarding the ability of retrogradely infused cardioplegic solution to perfuse the microvasculature of the heart. In this report, the microvascular distribution of retrogradely delivered cardioplegic solution was studied by means of a technique to quantitatively demonstrate capillary perfusion. Duroc piglet hearts were subjected to either antegrade (n = 4) or retrograde (n = 8) perfusion fixation with 2.5% glutaraldehyde and subsequently perfused with NTB-2 (an intracapillary marker). The results indicate that retrogradely delivered NTB-2 consistently perfused the anterior half of the intraventricular septum and the anterior and lateral free walls of the left ventricle but inconsistently perfused the posterior half of the intraventricular septum, the posterior wall of the left ventricle, and a small paraseptal region of the right ventricle. The remainder of the right ventricle was not perfused. In contradistinction, all regions of the heart were consistently perfused by the antegrade technique. In regions of the heart in which retrograde microvascular perfusion occurred, no statistical difference was found in the quantitative degree of capillary perfusion achieved by either the antegrade or retrograde technique. These results have important implications for planning strategies of myocardial protection and suggest that further investigation concerning the microvascular distribution of retrogradely delivered cardioplegic solution in human beings is merited.

Animals

Frequent amplification of the bcl-1 locus in poorly differentiated squamous cell carcinoma of the lung. The Lung Cancer Study Group.

The bcl-1 locus on chromosome 11 at band q13 has been shown to be rearranged in some chronic B lymphoid malignancies with the t(11;14)(q13;q32). Chromosome 11 abnormalities occur in solid tumors including squamous cell cancers and adenocarcinomas. We have recently reported the frequency amplification of the bcl-1 locus in squamous cell carcinomas of head and neck origin, and increased copy number also has been found in some breast adenocarcinomas. In this investigation, we analyzed the arrangement, copy number and expression of this locus in 111 primary non-small cell lung cancers. Bcl-1 was found to be amplified three- to 10-fold in seven fresh tumors. Whereas none of 51 adenocarcinomas showed bcl-1 amplification, six of 46 squamous cell carcinomas revealed an increase in bcl-1 copy number. This amplification was more frequently associated with larger and more poorly differentiated tumors. None of the cancers showed rearrangement of this locus.

Adenocarcinoma

Improved neonatal heart preservation with an intracellular cardioplegia and storage solution.

The optimal conditions for preservation of the neonatal heart for transplantation remain uncertain. An isolated, working neonatal piglet heart model was used to compare a standard extracellular-like cardioplegic solution followed by storage at 4 degrees C in normal saline for 12 hr (n = 8) to cardioplegia and storage at 4 degrees C for 24 hr in an intracellular-like solution (n = 7). Seven of eight hearts in the 12-hr Extracellular Group failed to regain function, with a maximum stroke work index (SWI), developed at a left ventricular end-diastolic pressure (LVEDP) of 9 mm Hg of 0.91 +/- 0.30 x 10(3) erg/g (mean +/- standard error of the mean), 7.1% of nonpreserved control hearts. In contrast, all hearts arrested and stored for 24 hr in the intracellular solution regained function with a maximum SWI, again at a LVEDP of 9 mm Hg of 9.51 +/- 1.98 X 10(3) erg/g, 73.7% of control (P less than 0.05). Ultrastructural changes seen by electron microscopy paralleled the functional results. We conclude that an intracellular arrest and storage solution may be superior to conventional solutions for extended preservation of the neonatal heart.

Animals

Surgical options for complex transposition of the great arteries.

Between September 1976 and November 1987, 53 patients underwent surgical treatment by the same surgeon for "complex transposition of the great arteries" with ventricular septal defect or severe left ventricular outflow tract obstruction, or both. Six patients with transposition and left ventricular outflow tract obstruction underwent atrial rerouting and direct relief of the left ventricular outflow tract obstruction. Twenty-two patients presented with transposition plus ventricular septal defect; 15 of these patients underwent atrial rerouting and ventricular septal defect closure and 7 underwent an arterial switch procedure. Twenty-five patients presented with transposition plus ventricular septal defect and left ventricular outflow tract obstruction, 23 of whom underwent a Rastelli procedure. There were one early death (mortality rate 1.9%; 90% confidence limits 0-7%) and three late deaths (mortality rate 5.8%) during a mean follow-up period of 42 months (range 2 to 124). These results show that 1) atrial rerouting is an appropriate surgical procedure for transposition of the great arteries with left ventricular outflow tract obstruction; 2) the arterial switch procedure provides excellent early correction of transposition with ventricular septal defect and is currently the preferred procedure for this lesion; and 3) the Rastelli procedure can be performed with a low early mortality rate and excellent long-term results for transposition with ventricular septal defect and left ventricular outflow tract obstruction.

Adolescent

Differential modification of morphine and methadone dependence by interferon alpha.

Subcutaneous implantation of a pellet of methadone was presented as a novel method for the establishment of physical dependence upon this agent and it was compared to (1) the state of physical dependence induced by multiple injections of methadone, administered over several days, and (2) the dependence established by injections of morphine and the implantation of a morphine pellet. Comparable signs of drug dependence were observed in rats treated with both morphine and methadone following the administration of the opiate antagonist naloxone. The administration of interferon-alpha significantly attenuated the severity of the withdrawal syndrome in dependent rats after chronic exposure to morphine and to a lesser extent after morphine and methadone in combination. In contrast, alpha interferon did not affect 6 of the 7 abstinence signs in animals dependent upon methadone alone. The observations suggest that the states of physical dependence upon morphine and methadone may be separate phenomena that involve different physiological mechanisms. Thus, interferon may be a useful adjunct in the treatment of subjects dependent upon morphine but not in those dependent on methadone.

Animals

3,4-Diphenyl-1H-pyrazole-1-propanamine antidepressants.

A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. Compounds were synthesized by Michael addition of acrylonitrile to diphenylpyrazole followed by reductive alkylation of the resultant diphenylpyrazolepropionitriles. Compound 3 was equipotent with imipramine in standard antidepressant assays in animals but showed no significant anticholinergic action and did not antagonize the antihypertensive effects of clonidine and guanethidine.

Animals

Parasympatholytic (anticholinergic) esters of the isomeric 2-tropanols. 2. Non-glycolates.

The 19 esters in Table I were prepared from (+)-2 alpha-tropanol, (-)-2 beta-tropanol, (+/-)-3-quinuclidinol, and a variety of non-glycolic acids in order to compare their central and peripheral activities with those of the glycolates reported in the previous paper. The results (Table II) showed that esters 6 and 17 were approximately equivalent to one another and to atropine, that 8 was equal in both central and peripheral activity to reference glycolates, that 9 and 19 were less active than 8 but 9 had a substantially reduced central activity, and that 10 and 11 were more active than the methoxy analogue reported earlier.

Animals