Analysis of premature ventricular counts in long term ECG following myocardial infarction.

Frequent and recurrent ventricular premature beats (VPB's) are considered to be associated with a higher risk of sudden cardiac death, particularly for survivors of myocardial infarction (MI). The distribution of VPB's has a large probability mass at zero, and a very heavy right hand tail. In this research, we fitted a model to VPB for patients for which VPB was present. The model was fitted on the basis of a relatively large data set on MI survivors in Israel. The model was fitted by a method which is based on the generalized linear model. This method, which was introduced by Zeger and Liang, is designed for longitudinal data and uses the quasi-likelihood concept. No specific assumptions are required on the shape of the distribution of the dependent variable. The results indicate that the model fits the data quite well but underestimates the very extreme high values. This research demonstrates the applicability of generalized linear models for longitudinal non-Gaussian data. Such data often arise in medical studies. The study also points out the distributional properties of VPB counts. In particular, it shows their associations with simple clinical and epidemiological variables, and with certain time periods during the day.     

Epidural block for obstetrics: Comparison of bolus injection of local anesthetic with gravity flow technique

Study Objective: To test the hypothesis that slow administration of local anesthetic into the epidural space by gravity flow reduces the incidence of signs and symptoms of unintended injection.

Design: Prospective, randomized study.

Setting: Teaching hospital.

Patients: 600 ASA physical status I and II parturients scheduled for labor and delivery or elective cesarean section.

Interventions: After identification of the epidural space with pulsations of an air-fluid column, parturients for vaginal delivery (n = 380) were randomized to receive a test dose of 3 ml 3% 2-chloroprocaine with epinephrine 20 μg, two doses of 7 ml bupivacaine 0.03 % with sufentanil 1 μg/ml and epinephrine 2 μg/ml by either gravity flow (Group 1) given over 30 seconds or by bolus injection (Group 2) given over 5 seconds through the epidural needle; parturients for Cesarean delivery (n = 220) were randomized to receive a test dose and two doses of 6 ml lidocaine 2 % with sufentanil 1 μg/ml and epinephrine 2 μg/ml by either gravity flow or by bolus injection through the epidural needle. Changes in maternal heart rate (HR) and blood pressure, signs of intravascular injection, and adverse effects of epidural bupivacaine-sufentanil were recorded after each dose.

Measurements and Main Results: Gravity flow administration (Group 1) was associated with a smaller increase in mean maternal HR (p < 0.001), less hypotension (p < 0.01), sedation (p < 0.01), nausea (p = 0.01), and segmental spread (p < 0.0001) than were corresponding doses given by traditional bolus injection (Group 1) for vaginal or Cesarean deliveries. The incidence of systemic toxicity was zero of 300 (0%) with gravity flow and 4 of 300 (1.3%) by bolus injection, p = 0.12, Fisher's exact test. No patient in either group had an accidental intrathecal injection.

Conclusion: Gravity flow administration of local anesthetic-opioid solution during epidural block for obstetrics was associated with fewer signs of systemic drug absorption and cardiovascular perturbations than was the traditional bolus injection. This study supports the current opinion that slow administration of local anesthetic during epidural black contributes to fewer adverse events.     

Single breath-holding scans of the abdomen using FISP and FLASH at 1.5 T

Single breath-holding gradient echo techniques fast imaging with steady-state free precession (FISP) and fast low angle shot (FLASH) images were evaluated in the study of the abdomen in 16 patients (13 liver, two kidney, and one pancreas examinations). Gradient echo images were compared retrospectively with conventional spin echo images for image quality (depiction of pathology and representation of anatomic detail), and contrast characteristics were evaluated. All lesions were shown on gradient echo images, and in three of 16 cases gradient echo images were more diagnostic than spin echo images. On both FISP and FLASH images, most hepatic metastases were hyperintense relative to normal liver. The predicted flip angles for maximal contrast for the liver were modeled from signal intensity equations for FISP and FLASH and yielded predicted flip angles of approximately 40-55 degrees for FISP and 15-25 degrees for FLASH. Peak signal-to-noise ratio in liver of normal volunteers occurred at approximately 30 degrees for both FISP and FLASH. Single breath-holding gradient echo images are useful in the evaluation of abdominal structures and this study provides a framework for future work.     

Evolution of immune surveillance and tumor immunity: studies in Xenopus

Summary: We have developed a novel experimental model of cancer immunity in the frog, Xenopus , which may provide a useful alternative to murine tumor models and a way to assess whether the control of tumor development is a fundamental function of the immune system of vertebrates. In Xenoptis , tumor immunity can be studied in two developmentally distinct immune systems. The larval immune system reflects characteristics of an ancestral system that appears to function without classical MHC class I antigen presentation and an efficient effector mechanism. The adult system appears more highly evolved in that it is remarkably similar to that of mammals and is able to generate a potent antitumor response. This amphibian model also provides a unique system with which to investigate a postulated role of heat shock proteins as components of an ancestral system of antigen presentation and/or immune surveillance that predates the antigen presentation pathway that exclusively involves MHC molecules.     

Replacement of cholesterol gallstones by murideoxycholyl taurine gallstones in prairie dogs fed murideoxycholic acid

The effect of two hydrophilic bile acids, murideoxycholic acid (3 alpha,6 beta-dihydroxy-5 beta-cholanoic acid) and ursodeoxycholic acid, on cholesterol and bile acid metabolism and hepatic pathology and gallstone composition was studied in the prairie dog. Cholesterol gallstones were induced by feeding a diet containing 1.2% cholesterol for 75 days. The animals were divided into six groups, and gallstone regression was studied as follows: groups 2 and 5, chow plus 0.2% cholesterol; groups 3 and 6, chow plus 0.2% cholesterol plus 0.15% ursodeoxycholic acid; groups 4 and 7, chow plus 0.2% cholesterol plus 0.15% murideoxycholic acid. Animals in groups 2 to 4 were killed after an additional 6 wk; animals in groups 5 to 7 were killed after an additional 12 wk. Gallstone dissolution did not occur in any group. The gallstones in groups 2, 3, 5 and 6 were typical cholesterol aggregates, as determined by polarized light microscopy and Fourier transform infrared spectrometry. The gallstones of the murideoxycholic acid group were large, solitary, dark stones that appeared radiopaque under 22 kVp x-ray examination. Scanning electron microscopy showed that in these stones the cholesterol crystals had been replaced by an amorphous material, both within the stone and on the stone surface. Chemical analysis indicated that at the end of 12 wk the calcium/sodium salt of the taurine conjugate of murideoxycholic acid (murideoxycholyl taurine) comprised 70% of the stones; protein, cholesterol and small amounts of other bile salts were also present. In vitro studies confirmed the insolubility of the sodium and calcium salts of murideoxycholyl taurine. These studies indicate that the hydrophilic bile acids, murideoxycholic acid and ursodeoxycholic acid, did not achieve gallstone dissolution under the conditions used. In the animals fed murideoxycholic acid, an insoluble calcium salt of murideoxycholyl taurine replaced cholesterol as the major constituent of gallbladder stones. This is the first example of an insoluble dihydroxy taurine-conjugated bile acid; administration of the unconjugated bile acid induced precipitation of a kind of gallstone not previously reported. The final result was transformation of cholesterol stones to bile salt stones.     

Repeat hepatic resections for metastatic colorectal cancer.

OBJECTIVE: The authors weighed the risks and benefits of repeat liver resections for colorectal metastatic disease. METHOD: In the 6-year period between January 1985 and June 1991, 499 patients underwent liver resections for colorectal metastases at the Memorial Sloan-Kettering Cancer Center. Of these, 25 patients had repeat surgical resections for isolated recurrent disease to the liver. The clinical data for these patients were reviewed. RESULTS: The median interval between the two resections was 11 months. There were no perioperative deaths, and the complication rate was 28%. Median follow-up after the second liver resection is 19 months, with median survival of 17 months for nonsurvivors. Although the median survival after the second resection is 30 months, 20 of the 25 patients have had recurrences with a median disease-free interval of only 9 months. No characteristic of primary or metastatic disease predicted outcome, including time between presentation of the primary and development of liver metastases, disease-free interval after the first liver resection, and bilobar liver involvement. CONCLUSIONS: Although repeat liver resections can be performed safely and improves survival, the likelihood of cure from such resection therapy is low. This likelihood of further recurrences encourage studies of adjuvant or alternative treatments of this population.     

Early laparoscopic cholecystectomy for acute cholecystitis

Background: The timing of laparoscopic cholecystectomy for acute cholecystitis remains controversial. Methods: One hundred ninety-four patients with acute cholecystitis were reviewed. The conversion rates for the various number of days of symptoms before surgery were analyzed. The conversion rate dramatically increased from 3.6% for those patients with 4 days of symptoms to 26% for those patients with 5 days of symptoms. The mean number of days of symptoms prior to surgery in those patients who underwent successful laparoscopic cholecystectomy was 4.1 as compared to 8.0 in those patients who required open cholecystectomy (p < 0.0001). Based on this data the patients were divided into two groups. Group 1 consisted of 109 patients who underwent laparoscopic cholecystectomy within 4 days of onset of symptoms and group 2 consisted of 85 patients who underwent laparoscopic cholecystectomy after more than 4 days following onset of symptoms. Results: The conversion rate from laparoscopic to open cholecystectomy was 15%. The conversion rate for group 1 was 1.8% as compared to 31.7% for group 2 (p < 0.0001). Indications for conversion were inability to identify the anatomy secondary to inflammatory adhesions (68%), cholecystoduodenal fistula (18%), and bleeding (14%). The major complication rate for group 1 was 2.7% as compared to 13% for group 2 (p= 0.007). The mortality rate for all patients with attempted laparoscopic cholecystectomy for acute cholecystitis was 1.5%. The average procedure time for group 1 was 100 ± 37 min vs 120 ± 55 min in group 2. The average number of postoperative hospital days in group 1 was 5.5 ± 2.7 days as compared to 10.8 ± 2.7 days in group 2. Conclusions: We advocate early laparoscopic cholecystectomy within 4 days of onset of symptoms to decrease major complications and conversion rates. This decreased conversion rate results in decreased length of procedure and hospital stay. Received: 28 March 1996/Accepted: 12 September 1996     

Neurotoxicity after spinal anaesthesia induced by serial intrathecal injections of magnesium sulphate An experimental study in a rat model

We have previously demonstrated in a rat model that the lumbar intrathecal injection of 0.02 ml 6.3% magnesium sulphate, a concentration iso-osmolar with rat plasma, produces a state of spinal anaesthesia and general sedation which reversed completely after 6 h, without evidence of neurotoxicity, immediately or during the week thereafter. Using the same model and five groups of six animals in each, we administered the same volume and concentration of magnesium sulphate and compared its clinical effects with those of 0.02 ml 12.6% magnesium sulphate, 0.02 ml 2% lignocaine and 0.02 ml 0.9% sodium chloride solution, given as a series of 15 injections on alternate days for a period of 1 month. The animals were then killed and their spinal cords and meninges examined histologically. No significant differences were noted in the times of onset, durations of sensory and motor blockade and the times to full recovery throughout the entire period of 1 month's observation in the animals receiving intrathecal 6.3% magnesium sulphate. In the group receiving 12.6% magnesium sulphate, the time of onset of sensory and motor blockade was shorter and the duration of both parameters was significantly longer than in the former group. Full clinical recovery and resumption of normal eating and drinking took place in both groups throughout the entire series of 15 successive intrathecal injections. Identical, mild, uniform histopathological changes in the spinal cord were seen in all the five groups, including the group in which only the intrathecal catheter was implanted. The complete recovery and benign consequences of repeated intrathecal injections of iso-osmolar magnesium sulphate in a rat model indicate a lack of neurotoxicity and provide an impetus for further trials in larger animal species, before initial clinical trials of this substance, given intrathecally, in humans.