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Divergent effects of serotonin on coronary-artery dimensions and blood flow in patients with coronary atherosclerosis and control patients BACKGROUND. Studies in animals have shown that serotonin constricts coronary arteries if the endothelium is damaged, but in vitro studies have revealed a vasodilating effect on isolated coronary segments with an intact endothelium. To investigate the effect of serotonin in humans, we studied coronary-artery cross-sectional area and blood flow before and after the infusion of serotonin in seven patients with angiographically normal coronary arteries and in seven with coronary artery disease. METHODS. We measured the cross-sectional area of the coronary artery by quantitative angiography and coronary blood flow with an intracoronary Doppler catheter. Measurements were obtained at base line and during intracoronary infusions of serotonin (0.1, 1, and 10 micrograms per kilogram of body weight per minute, for two minutes). We repeated the measurements after an infusion of ketanserin, an antagonist of serotonin receptors that is thought to block the effect of serotonin on receptors in the arterial wall but not in the endothelium. RESULTS. In patients with normal coronary arteries, the highest dose of serotonin increased cross-sectional area by 52 percent (P less than 0.001) and blood flow by 58 percent (P less than 0.01). The effect was significantly potentiated by administration of ketanserin. In patients with coronary-artery atherosclerosis, serotonin reduced cross-sectional area by 64 percent (P less than 0.001) and blood flow by 59 percent (P less than 0.001). Ketanserin prevented this effect. CONCLUSIONS. Serotonin has a vasodilating effect on normal human coronary arteries; when the endothelium is damaged, as in coronary artery disease, serotonin has a direct, unopposed vasoconstricting effect. When considered with other evidence, these data suggest that platelet-derived factors such as serotonin may have a role in certain acute coronary ischemic syndromes.
Experimental obliterative cholangitis. A model for the study of biliary atresia. Noninfectious obliterative cholangitis results from biliary tract inflammation in clinical conditions such as biliary atresia and sclerosing cholangitis. The purpose of this study was to develop an animal model of noninfectious biliary tract inflammation and fibrosis. An implantable osmotic pump was connected to a catheter placed into the gallbladder of hamsters. Phorbol myristate acetate (PMA) was infused into the biliary tract for periods of 6 hours to 28 days. After 7 days the animals developed neutrophil infiltration, cellular necrosis, and edema of the biliary ducts. After 14 days, the animals demonstrated intrahepatic cholestasis with bile duct fibrosis and acute and chronic inflammatory cell infiltration. By 28 days pronounced portal fibrosis was present, some of which created an early bridging cirrhosis pattern. In addition there was evidence of neocholangiogenesis. We conclude that long-term PMA infusion into the biliary tract generates an inflammatory response characterized by obliterative cholangitis and fibrosis, sharing many of the histologic features of human biliary atresia. This model may provide a relatively simple technique for investigating the process of nonpyogenic biliary tract inflammation.
Effects of milrinone on pulmonary vasculature in normal dogs and in dogs with pulmonary hypertension. OBJECTIVE: To study the effects of milrinone on pulmonary vasculature. BACKGROUND: It has been suggested that bipyridines or their derivatives may have a selective pulmonary vasodilation effect. METHODS: Preliminary study: milrinone administration to 12 normal dogs (low dose [bolus 75 micrograms/kg for 5 min followed by a continuous infusion at 0.75 micrograms/kg.min, n = 6]; high dose [bolus 150 micrograms/kg for 5 min followed by continuous infusion at 1.5 micrograms/kg.min, n = 6]). Main study: milrinone administration to 18 dogs with pulmonary hypertension due to pulmonary embolism induced by a massive injection of autologous muscle cubes. The pulmonary hypertension dogs were divided into three groups: a) group E (n = 6) received embolization only, as control; b) group L (n = 6) received low-dose milrinone; and c) group H (n = 6) received high-dose milrinone, equivalent to the preliminary study group. Hemodynamic measurements and blood samplings were obtained at baseline and at 15, 30, and 60 min after start of milrinone infusion. RESULTS: Milrinone did not change mean pulmonary artery pressure (MPAP) in normal dogs. Milrinone decreased MPAP significantly in dogs with pulmonary hypertension. Pulmonary vascular resistance index remained at an almost constant level in normal dogs, but decreased significantly in dogs with pulmonary hypertension. Mean arterial pressure was maintained at a constant level in all groups. High-dose milrinone administration decreased systemic vascular resistance index (SVRI) significantly; low-dose milrinone administration decreased SVRI slightly. CONCLUSIONS: Milrinone may have a selective pulmonary vasodilatory effect only in dogs with pulmonary hypertension. The mechanism that produced a selectivity on pulmonary vasculature in dogs with pulmonary hypertension is unknown. However, an inhibition of platelet aggregation may decrease the MPAP resulting from an increase in cAMP caused by milrinone. Further studies are needed to resolve the pulmonary vasodilatory effect of milrinone in dogs with pulmonary hypertension.
Sudden cardiac death during exercise in a weight lifter using anabolic androgenic steroids: pathological and toxicological findings. A 21-year-old, previously healthy weight lifter collapsed during a bench press workout. He had taken anabolic androgenic steroids parenterally for the previous several months. Pertinent autopsy findings included marked cardiac and renal hypertrophy and hepatosplenomegaly, with regional myocardial fibrosis and focal myocardial necrosis. Nandrolone (19-nor-testosterone) metabolites were identified in postmortem urine. The possible etiologies of the cardiac findings are discussed.
The influence of drug interval on the effect of methotrexate and fluorouracil in the treatment of advanced colorectal cancer The importance of the interval between methotrexate (MTX) and fluorouracil (5-FU) was studied in 168 patients with previously untreated, measurable, advanced colorectal cancer. They were randomized to receive MTX 200 mg/m2, followed by 5-FU 600 mg/m2 either 24 hours (arm A) or 1 hour (arm B) after MTX. All patients received leucovorin (LV) 24 hours after MTX, 10 mg/m2 orally every 6 hours for six doses. The regimen was repeated every 2 weeks, with 5-FU escalation as tolerated. Arm A was significantly better than arm B with respect to overall response rate (29% v 14.5%, P = .026), time to progression (TTP; median, 9.9 months v 5.9 months, P = .009), and survival (median, 15.3 months v 11.4 months, P = .003). Significant differences between arms were not found in response rate, median TTP, or median survival for the subgroup of patients with rectal primaries who comprised 20% of the patients in each arm. Significant factors prognostic for survival were performance status and number of metastases, as well as treatment. Age did not influence survival. Toxicity was similar in both arms and was primarily gastrointestinal. More mucositis was seen in arm A. There were four toxic deaths secondary to neutropenia and infection (one from arm A and three from arm B) and three other deaths (two from arm A and one from arm B) that were possibly drug-related. The combination of MTX with LV rescue and 5-FU is an active regimen in advanced colorectal cancer; its efficacy is increased in colon, but not rectal cancer, when the interval between MTX and 5-FU is long (24 hours) rather than short (1 hour).
Low-dose bupivacaine does not improve postoperative epidural fentanyl analgesia in orthopedic patients [published erratum appears in Anesth Analg 1991 May;72(5):718] Epidural infusions of 10 micrograms/mL fentanyl combined with low-dose bupivacaine (0.1%) were compared with epidural infusions of fentanyl alone for postoperative analgesia after total knee joint replacement. There were no detectable differences between the two groups in analgesia (visual analogue scale ranging between 15 and 40 mm), infusion rates (which averaged 7-9 mL/h), or serum fentanyl levels (which reached 1-2 ng/mL). The incidence of side effects, including nausea, vomiting, and pruritus, was also similar. Of the patients receiving fentanyl and low-dose bupivacaine, one developed a transient unilateral motor and sensory loss, and one developed significant hypotension and respiratory depression. The addition of low-dose bupivacaine does not improve epidural fentanyl infusion analgesia after knee surgery and may increase morbidity.
Cytologic identification of clinically occult proliferative breast disease in women with a family history of breast cancer. A cytologic method for sampling the normal breast by fine-needle aspiration (FNA) was used to determine the frequency of clinically inapparent proliferative breast disease (PBD) in women with family histories of breast cancer. The authors attempted to obtain specimens from each quadrant of both breasts in 51 female first-degree relatives of breast cancer patients. The study group had no detectable masses by physical examination or mammography. Samples were prepared on membrane filters, Papanicolaou stained, and evaluated cytomorphologically. Three hundred seventy-eight of 408 (92.6%) possible quadrants were sampled; cellular material was obtained from 290 (76.7%) quadrants. PBD was identified in 20 of the 51 women (39.2%). When epithelium was obtained, nuclear area, perimeter, and diameter were measured with the use of computerized image analysis. Nuclei in samples containing atypical hyperplasia showed significant differences in these parameters when compared with cells from samples containing normal epithelium or benign hyperplasia. The authors' findings indicate that FNA sampling and computerized image analysis are useful in the detection and characterization of clinically inapparent PBD.
Acute porphyria presenting with hyperamylasemia. An elevation of serum amylase and lipase has not been reported previously to occur with porphyria. In this report, we describe a patient who presented with the clinical and laboratory picture of pancreatitis: elevated amylase, lipase, amylase-creatinine clearance ratio, and with abdominal pain. Only after extensive evaluation, was the patient found to have porphyria. On two separate occasions, with hematin therapy, her serum amylase decreased, as did her clinical symptoms of porphyria and her urinary quantitative porphyrins. This suggests an association between elevation of the serum amylase and lipase with acute porphyria. Moreover, this association can lead to delay in establishing the diagnosis of acute porphyria.
Maternal serum alpha-fetoprotein screening: further consideration of low-volume testing. Unrecognized assay drift that may occur during low-volume (fewer than 500 specimens per week) maternal serum alpha-fetoprotein testing could result in either underestimation or overestimation of the number of pregnant women who are at increased risk of fetal malformations and genetic anomalies. Quality control software programs that incorporate the use of a multirule Shewhart chart are designed to detect assay drift. Careful selection of quality control sera for inclusion in analytic assays and appropriate application of a multirule quality control procedure to values that are obtained on these control materials should detect assay drift, regardless of the volume of patients' specimens in the run.
Inhibition of neutrophil migration by tumor necrosis factor. Ex vivo and in vivo studies in comparison with in vitro effect. Coincubation of neutrophils with TNF inhibited the chemoattractant-directed migration of neutrophils under agarose and enhanced their migration in the multiwell chemotaxis chamber. To assess the physiological significance of these differing in vitro TNF effects, ex vivo and in vivo investigations were performed using animal models. Neutrophils from the peripheral blood of rabbits preadministered systemic TNF showed impaired ability to migrate toward chemoattractants in vitro. In addition, systemic TNF administration suppressed zymosan-activated plasma-induced local accumulation of leukocytes in mouse skin. The results indicate that circulating TNF may act as a suppressor for local inflammatory reaction.
Microsurgical epididymovasostomy by tubule intussusception: a new technique in rat model. This experimental study on 15 adult male rats with bilateral epididymovasostomies evaluates a new technique of tubule intussusception as an improved form of end-to-end anastomosis. This paper describes in detail the steps in this technique and offers physiological, anatomical, and histological follow-up after 3 months. With this technique there is a 97% patency rate and a 23.3% incidence of macroscopic spermatic granuloma. Complications are discussed in detail.
Irrigation device for neuroangiographic procedures. A simple irrigation device for use in diagnostic and interventional neuroangiographic procedures is described. The device is used to flush bubbles and blood clots from catheter hubs. The authors also describe a technique in which this device can be used to prevent filling a catheter with air when a guide wire is removed.
Long-term experience with a totally implanted catheter system in cancer patients. Long-term experience with totally implanted catheter systems (TICS) is limited. We retrospectively evaluated the performance and long-term complications of TICS for intravenous infusion in cancer patients; 134 systems were implanted in 128 patients. The median duration of implantation was 144 weeks with 49 systems implanted for more than one year. Complications related to surgical factors included malposition of reservoir (2%), skin perforation or wound dehiscence (1.5%) and pneumothorax (less than 1%). Complications not related to surgical factors included: drug extravasation (1.5%), mechanical malfunction (1.5%), vein thrombosis (less than 1%), clotting of the reservoir or catheter (2%), skin infection (1.5%), and sepsis (less than 1%). The total complication rate was 13%. Most complications resolved spontaneously or with medical treatment and only 6 patients (4.6%) required re-implantation of a second system. We conclude that with long-term usage of TICS, the complication rate remains low, making it a safe and viable alternative for patients requiring long-term intravenous therapy.
Exocrine pancreatic function in chronic liver diseases. To confirm the respective influence of chronic alcoholism and liver disease on exocrine pancreatic function in cholecystokinin secretin (CS), tests were performed on patients with chronic liver cirrhosis (LC) and non-cirrhotic (nLC) disease of alcoholic (A) and nonalcoholic (nA) etiology. Results were compared in four subgroups (ALC, N = 26; AnLC, N = 45; nALC, N = 18; and nAnLC, N = 43). Volume of duodenal juice and bicarbonate output (BO) were increased and maximal bicarbonate concentration was decreased in ALC, compared with those in normal controls. Comparison of LC and nLC indicated that the volume, BO, and amylase output (AO) were greater in LC than in nLC of alcoholic etiology, but not in those of nonalcoholic etiology. The initial disappearance rate (KICG) of indocyanine green (ICG) excretion correlated with a parameter of CS test in alcoholic liver disease (vs. volume: r = -0.51, p less than 0.01 vs BO: r = -0.40, p less than 0.01), but not in nonalcoholic liver disease. Concurrent chronic pancreatitis with pain and definite exocrine insufficiency was observed in only one ALC patient and in four AnLC patients, but in none of the nonalcoholics. In alcoholic liver disease, exocrine pancreatic secretion tends to increase with severity of liver damage, but concurrence of definite chronic pancreatitis is not correlated with the severity.
Left ventricular filling impairment in asymptomatic chronic alcoholics. Systolic left ventricular dysfunction is relatively common in even asymptomatic alcoholics, but whether diastolic function is also altered is much less well-studied. We used M-mode and Doppler echocardiography to study left ventricular size, mass, systolic function and diastolic filling in 32 alcoholics free of clinically detectable heart disease and in 15 healthy control subjects. Left ventricular mass index and posterior wall thickness were higher in alcoholics than in controls, but there was no statistically significant difference either in end-diastolic size or in systolic ventricular function. More abnormalities were found in the Doppler indexes of diastolic function, however. The alcoholics had a prolonged relaxation time (200 +/- 6 vs 184 +/- 5 ms [mean +/- standard error], p less than 0.05), a decreased peak early diastolic velocity (52 +/- 2 vs 60 +/- 3 cm/s, p less than 0.05), a slower acceleration of the early flow (410 +/- 18 vs 552 +/- 43 cm/s2, p less than 0.01), and a higher atrial-to-early peak velocity ratio (0.74 +/- 0.04 vs 0.60 +/- 0.05, p less than 0.05). This pattern of changes suggests a primary abnormality in the relaxation of the left ventricle. In multivariate analyses, the abnormalities in the Doppler indexes were independent of the duration of alcoholism, the quantity of the most recent ethanol exposure and the increased mass of the left ventricle. Impaired early filling of the left ventricle due to delayed relaxation is common in asymptomatic alcoholics and may in fact be the earliest functional sign of preclinical alcoholic cardiomyopathy.
Reevaluation of manometric criteria for vigorous achalasia. Is this a distinct clinical disorder? Clinical and manometric data from 97 consecutive patients with idiopathic achalasia were analyzed to see if a distinct subset with vigorous achalasia could be identified. Statistical analyses failed to detect a unique group of subjects based on the distribution of contraction wave amplitudes alone. Because of this, patients falling above the 95th percentile (N = 4, mean wave amplitude greater than 100 mm Hg for each) were compared with those having mean amplitudes above the conventional threshold for the diagnosis of vigorous achalasia (mean amplitude 60-100 mm Hg, N = 4), and with the remainder (N = 89, mean amplitude less than 60 mm Hg). Subjects with mean amplitudes less than 60 mm Hg and with mean amplitudes 60-100 mm Hg closely resembled each other in all measured clinical features, whereas subjects with mean amplitudes greater than 100 mm Hg were all male, were older (67 +/- 4 years vs 47 +/- 2 years; P less than 0.01), and appeared to have somewhat longer duration of symptoms when compared with the remainder (82 +/- 41 vs 44 +/- 10 months; P = 0.4). Chest pain and other esophageal symptoms, basal and residual lower sphincter pressures, and response to first treatment did not differ among the three groups. These data indicate that high-fidelity manometry techniques identify a rare subset of achalasia patients with mean contraction amplitudes exceeding 100 mm Hg that, although older and possibly with greater duration of symptoms, presents similarly to others with idiopathic achalasia. Outcome from conventional treatment is also similar for the "vigorous" and "nonvigorous" patients, making the distinction of questionable value.
Interventional radiology of the biliary tract. Transcholecystic intervention. Diagnostic and therapeutic biliary intervention by percutaneous access to the gallbladder is an important new area in interventional radiology. The anatomy of the gallbladder, biliary tree, and surrounding viscera is reviewed in this article as a preliminary to discussion of the diagnostic techniques of aspiration, cholangiography, biopsy, and the therapeutic techniques of gallbladder drainage and cholelithotomy. Recently there has been a bewildering proliferation of procedures aimed at removal, fragmentation, and dissolution of gallbladder stones. Several of these are discussed in this article. Removal of common bile duct stones by percutaneous cholecystostomy also is discussed.
Comparison of silent and symptomatic ischemia during exercise testing in men OBJECTIVE: To compare angina and ST-segment depression during exercise testing, as markers for coronary artery disease. DESIGN: Retrospective analysis of exercise test responses and cardiac catheterization results. SETTING: A U.S. Veterans Affairs medical center. PATIENTS: Four hundred and sixteen men who were referred for the evaluation of symptoms, postmyocardial infarction testing, or both. Two hundred patients had no clinical or electrocardiographic evidence of previous myocardial infarction, whereas 216 were survivors of a previous myocardial infarction. INTERVENTIONS: All patients did a standard exercise test and had diagnostic coronary angiography with ventriculography within an average of 32 days (range, 0 to 90 days) of their exercise test. RESULTS: Two hundred patients without a previous myocardial infarction were divided into four groups: the no ischemia group had 80 patients; the angina pectoris only group had 23 patients; the silent ischemia group had 40 patients; and the ST-segment depression and angina pectoris group had 57 patients. In patients without a previous myocardial infarction, exercise-induced ST-segment depression was a better marker than exercise-induced angina for the presence of any coronary artery disease (P less than 0.005). Patients with symptomatic exercise-induced ischemia had a higher prevalence of severe coronary artery disease than did those with only silent ischemia (30% compared with 20%; 95% CI, - 7.3% to 27.0%; P = 0.005). For the 216 survivors of a myocardial infarction, divided into the same four groups, ST-segment depression again was a better marker for the presence of severe coronary artery disease compared with angina alone (P = 0.08). The prevalence rates of severe coronary artery disease in the no ischemia plus myocardial infarction group, the angina pectoris only plus myocardial infarction group, the silent ischemia plus myocardial infarction group, and the ST-segment depression and angina pectoris plus myocardial infarction group were 10%, 9%, 23%, and 32%, respectively (P less than 0.01). CONCLUSIONS: Exercise-induced ST-segment depression is a better marker for coronary artery disease than is exercise-induced angina. Symptomatic ischemia during the exercise test is a better marker for severe coronary artery disease than is silent ischemia.
Capsular genu syndrome. We report 5 patients with unilateral infarct and 1 with hemorrhage limited to the genu of the internal capsule. The most prominent finding was contralateral facial and lingual hemiparesis with dysarthria. Three patients also showed unilateral mastication-palatal-pharyngeal weakness, and 1 had unilateral vocal cord paresis. Mild limb involvement was limited to hand weakness in 4 patients. Our findings suggest that the majority of motor corticopontine and corticocobulbar fibers are located in the genu of the internal capsule. The faciolingual syndrome and its variants are highly suggestive of capsular genu stroke.