Changing physicians' behavior.
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Biomedical subjects
Publications and source records attributed to J Metzger.
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One hundred twenty-nine patients were prospectively studied after a first myocardial infarction. A first signal-averaged electrocardiogram (SAECG-1) was performed in the acute phase (within 48 hours after onset of symptoms) and a second one (SAECG-2) in the late phase (6 to 18 months after hospital discharge). We studied the influence of nine parameters on the evolution of the signal-averaged electrocardiogram: age, gender, myocardial infarction location, number of diseased coronary vessels, infarct-related coronary artery patency, use of thrombolytic therapy or percutaneous transluminal coronary angioplasty in the acute phase, left ventricular ejection fraction, and recurrence of ischemic events. No follow-up data were available in 15 patients. Of the remaining 114 patients, an ischemic event occurred in 25 (22%). The signal-averaged electrocardiogram remained unchanged in 97 (85%) (remaining normal in 78 and abnormal in 19). It became abnormal in 13 (11.5%) and became normal in 4 (3.5%). In patients with a normal SAECG-1, two factors were associated with the change to an abnormal SAECG-2: (1) an ischemic event occurred in 11 (85%) of 13 patients whose SAECG-2 was abnormal compared with only 13 (17%) of 78 patients whose SAECG-2 remained normal (p < 0.0001), and (2) 100% of patients with an abnormal SAECG-2 had an inferior myocardial infarction compared with 54% of patients with a normal SAECG-2 (p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)
Two lipopeptide analogues of the Escherichia coli lipoprotein rendered water-soluble by polyoxyethylene were tested for mitogenicity in vitro in murine and human B lymphocytes and for adjuvant activity in vivo in mice. These highly amphiphilic lipopeptides retained the biological activity other lipopeptides usually exerted which supports the hypothesis of specific interactions of lipopeptides with membranes of reactive cells. The activation of human B lymphocytes by these lipopeptides was much less pronounced compared to that of murine cells. However, given in combination with anti-CD40 antibodies plus interleukin-4, human B lymphocytes could synergistically be stimulated to proliferate. As an adjuvant, the polyoxyethylene linked lipopeptides were almost as potent as Freund's adjuvants and other basic lipopeptides. Being water-soluble, these novel analogues are easy to apply and they are suitable for field studies as adjuvants when sonication can not usually be provided.
We report on the 1-year follow-up after laparoscopic cholecystectomy in a consecutive series of 116 unselected patients. So far no such follow-up data have been published. The follow-up rate was 94%. All patients have been personally assessed on the base of a standardized follow-up form either at the hospital (58%) or by the general practitioner (42%). Using an adapted modified Visick classification we have found an excellent or good result in 96% of the patients. Although there were some minor dyspeptic complaints and a few abnormal laboratory findings no patient had a suspicion of residual or recurrent gall stones. There has been no reoperation. In conclusion laparoscopic cholecystectomy yields very satisfactory short-term results 1 year after operation even in an unselected population of patients.
The need for a routine preoperative intravenous cholangiogram (IVC) has been controversially discussed. We decided to assess if preoperative criteria such as history, clinical examination or laboratory findings could be used for selective indication for preoperative IVC. In a series of 146 patients with a preoperative IVC before undergoing laparoscopic cholecystectomy, history, clinical findings and laboratory results (bilirubin, transaminases, alkaline phosphatase, amylase) have been correlated with the radiological findings. ERCP was taken as the standard to assess the value of IVC. A normal IVC was quite reliable in excluding any pathology of the bile ducts or common bile duct stones. Thus specificity reached 96% and the negative predictive value was 97%. On the other hand a pathological IVC proved not to be a valid predictor of true pathological alterations. Sensitivity was only 60% and the positive predictive value just 55%. Over all accuracy was quite satisfactory (94%). We could not find a correlation between history, clinical or laboratory findings and the final result as assessed by ERCP. Therefore we could not find any useful parameters to define a selective policy for indication of preoperative IVC. On the other hand the IVC still proved useful to exclude relevant pathological findings. At the time being there is no strong argument for abandoning routine preoperative IVC.
The 12-lead electrocardiograms of 50 patients with 1 anterogradely conducting accessory pathway were analyzed to obtain characteristics of electrocardiographic findings in the midseptal, anteroseptal, true posteroseptal and right free wall accessory pathway locations. Locations were confirmed by surgery (33 patients) or radiofrequency catheter ablation (17 patients). This study analyzed (1) QRS in the frontal plane, (2) delta wave axis in the frontal plane, (3) the angle between QRS and delta wave axes, (4) the R/S ratio in lead III, (5) negativity of delta wave in inferior leads, and (6) the R/S ratio in precordial leads.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular (LV) function was studied in 30 patients with lone atrial fibrillation (AF) (paroxysmal [n = 27] and persistent [n = 3]) before and after ablation of atrioventricular conduction. In all patients, drug treatment did not control ventricular rate during AF or prevent recurrences of the arrhythmia, or both. LV ejection fraction, and LV end-systolic and end-diastolic, and left atrial dimensions were measured by echocardiography before (mean 7 +/- 10 months, range < 1 to 37) and after (14 +/- 20 months, < 1 to 77) ablation. Before ablation, LV ejection fraction was < or = 50% in 12 patients (group I) and > 50% in 18 (group II). After ablation, LV ejection fraction increased significantly in group I from 43 +/- 8% to 54 +/- 7% (p < 0.0001). There were also significant decreases in LV-end systolic and end-diastolic, and left atrial dimensions. No changes in these parameters were observed in group II. Groups I and II had a significant difference in the duration of AF (group I: mean 11 years, range 8 to 28; and group II: 5 years, 2 to 14) (p < 0.05). No difference was present in age, sex, New York Heart Association functional class for dyspnea, or type of ablation procedure. Thus, some patients with lone AF may show deterioration of LV function, which appears to be related to the duration of the arrhythmia; in these cases, LV function may improve significantly after ventricular rate control is accomplished by ablation of atrioventricular conduction.
One hundred twenty-nine patients were retrospectively analyzed and divided into 3 groups according to (1) the presence of a patent artery obtained either spontaneously or after thrombolytic therapy but without percutaneous transluminal coronary angioplasty (PTCA) (group I, n = 83), (2) the presence of a patent artery after opening by PTCA (group II, n = 29), or (3) absence of reperfusion despite thrombolytic therapy or PTCA (group III, n = 17). Thrombolytic therapy was given within 4 hours after onset of symptoms (mean 2.5 +/- 1.0 hours) and PTCA was performed within 24 hours after the onset of symptoms (mean 6 +/- 6 hours). Signal averaging was performed within 24 hours after cardiac catheterization. An abnormal signal-averaged electrocardiogram was present in 10 of 83 (12%) group I, 9 of 29 (31%) group II and 7 of 17 (41%) group III patients (p < 0.05 group I vs II, p < 0.01 group I vs III, no statistical difference group II vs III). Therefore, in contrast to reperfusion by thrombolytic therapy the incidence of abnormalities on the signal-averaged electrocardiogram early after myocardial infarction is not reduced by an early opening of the culprit vessel by PTCA.
We studied the relationship between wall motion abnormalities determined by echocardiography and the signal-averaged electrocardiogram in 82 consecutive patients during the acute phase of a first myocardial infarction. An abnormal signal-averaged electrocardiogram was defined as the presence of two of the following criteria: a QRS duration > or = 114 ms, a root mean square voltage (RMS) of the last 40 ms < or = 25 microV and an amplitude signal lower than 40 microV lasting > or = 39 ms. The left ventricle was divided into 13 segments and the contraction pattern divided into akinesia alone (including dyskinesia) (group A), hypokinesia alone (group B) and both hypokinesia and akinesia (group C). An abnormal signal-averaged electrocardiogram was found in 14/82 patients (17%) and was correlated with the persistence of occlusion of the infarct-related vessel (32% vs 9%, P < 0.02). In patients with a patent vessel, the incidence of an abnormal signal-averaged electrocardiogram was 14% in group A, 9% in group B and 0% in group C (NS). In patients with an occluded vessel an abnormal signal-averaged electrocardiogram was found in 10% of group A patients, in 36% in group B patients and in 75% of group C patients (P = 0.05). Our study suggests that the presence of hypokinetic areas during the acute phase of a first myocardial infarction and an abnormal signal-averaged electrocardiogram indicate an occluded infarct-related vessel.
Twelve dogs were divided into two groups of six each, and were infused with bis-3,5-dibromosalicyl fumarate stroma-free hemoglobin (DBBF-Hb) or albumin. Their responses to an intravenous bolus of Escherichia coli were followed for 4 hr. Bacterial clearance from the blood stream was studied using standard colony counting methodology as well as blood counts, blood chemistries, and clotting factor analysis. There was a significant difference in mean arterial pressure (MAP) over time between DBBF-Hb-treated dogs and those treated with albumin (P < 0.02). While the DBBF-treated dogs had a higher MAP during the 10 min of bacteremia, after 1 hr, there were no longer any appreciable differences between septic dogs treated with DBBF-Hb vs. albumin. Consumption of clotting and natural anticoagulant factors was observed to be similar in both groups, as were endotoxin levels. Blood urea nitrogen (BUN) increased slightly in both groups, while white blood cell counts and clotting factor levels fell in both groups in a similar fashion. There was a more pronounced fall (P < 0.04) in platelet counts in the animals treated with DBBF-Hb. In the dogs treated with DBBF-Hb, there was also a late rise in pCO2 (P < 0.01), a more pronounced fall in pO2, and greater acidosis, which suggested that ventilation perfusion abnormalities may have been exacerbated by DBBF-Hb treatment. Since the exacerbation of respiratory abnormalities was not related to diminished bacterial or endotoxin clearance, the possibility is raised that DBBF-Hb interferes with compensatory respiratory changes during sepsis.
A novel side reaction in Fmoc-solid-phase synthesis, which occurs during removal of protecting groups and detachment from the resin, was elucidated by investigations on model peptides: During the cleavage of Pmc- or Mtr-protecting groups from arginine residues by trifluoroacetic acid in peptides with O-tert-butyl-protected aliphatic hydroxyamino acids, peptides containing O3-sulfo-serine and O3-sulfo-threonine are formed as side-products in high yields, if suitable scavengers are absent. Subsequent to their isolation and purification, the structures of these peptide sulfuric acid mono-esters could unequivocally be proven by chemical and spectroscopic (MS, NMR, IR) methods.
Out of 110 patients suffering from gallstone-related symptoms, 21 underwent ERCP prior to laparoscopic cholecystectomy. Indications for this combined treatment were laboratory signs of cholestasis (36%), pancreatitis (29%), pathological IVC (18%), sonographic evidence for bile duct dilatation (10%) and cholangitis (7%). Local and general complications were not increased neither intraoperatively nor postoperatively. Median duration of postoperative hospital stay was four days for ERCP-treated patients as compared to three days for patients subjected to laparoscopic cholecystectomy only. In summary treatment of choledocholithiasis by a combination of preoperative ERCP and laparoscopic cholecystectomy offers the following advantages: high patient comfort, low incidence of complications and short hospitalization compares favourably with conventional common bile duct exploration.
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The primary structure of the alpha and beta subunits of phosphorylase kinase reveals that both proteins contain a carboxyl-terminal CA1A2X motif (where C is cysteine, A1 and A2 are aliphatic amino acids, and X is an uncharged amino acid), the recognition signal for a protein polyisoprenyltransferase. The product, a polyisoprenylated cysteine, can be detected by phenylthiocarbamoylamino acid analysis and by microsequencing following conversion to S-ethylcysteine. Mass spectrometry confirms a covalently linked farnesyl residue in both subunits. Tandem mass spectrometry localizes these modifications at the cysteine residues present in the carboxyl-terminal CAMQ and CLVS sequences of the alpha and beta subunits, respectively. Membrane association of phosphorylase kinase, probably mediated by these farnesyl residues, is discussed.
In human neutrophils, the synthetic lipopeptide, N-palmitoyl-S-[2,3- bis(palmitoyloxy-(2RS)-propyl]-(R)-cysteinyl-(S)-seryl-(S)-lysyl-( S)-lysyl-(S) -lysyl-(S)-lysine [Pam3CysSer(Lys)4], activates NADPH-oxidase catalyzed superoxide (O2-) formation through pertussis-toxin-sensitive and pertussis-toxin-insensitive mechanisms (Seifert, R., Schultz, G., Richter-Freund, M., Metzger, J., Wiesmüller, K.-H., Jung, G., Bessler, W. G. & Hauschildt, S. (1990) Biochem. J. 267, 795-802). We studied the effects of lipopeptides on differentiation of HL-60 leukemic cells. Pam3CysSer(Lys)4 enhanced phorbol-12-myristate-13-acetate-induced O2- formation (presumably through the expression of components of NADPH oxidase) in a concentration-dependent manner with a half-maximal effect at 100 ng/ml and a maximum at 1 microgram/ml. The effect of the lipopeptide was evident after 24 h and reached a plateau after 48 h. (2S,6S)-2-Palmitoylamino-6,7- bis(palmitoyloxy)heptanoyl-(S)-seryl-(S)-lysyl-(S)-lysyl-(S) -lysyl-(S)-lysine enhanced O2- formation as well. The effects of Pam3CysSer(Lys)4 were potentiated by dibutyryl cAMP, dimethyl sulfoxide, retinoic acid, 1,25-dihydroxyvitamin D3, interferon-gamma and tumor-necrosis-factor-alpha. Pertussis toxin, but not its B-oligomer, partially inhibited enhanced O2- formation induced by Pam3CysSer(Lys)4. O2- formation induced by arachidonic acid and gamma-hexachlorocyclohexane were more sensitive to inhibition by pertussis toxin than O2- formation induced by phorbol 12-myristate 13-acetate. Enhanced O2- formation induced by dibutyryl cAMP was not affected by pertussis toxin. Unlike ATP, histamine, prostaglandin E1 and the beta-adrenergic agonist, isoproterenol, Pam3CysSer(Lys)4 did not increase cytosolic Ca2+ [( Ca2+]i) in undifferentiated HL-60 cells. Histamine but not lipopeptides stimulated high-affinity GTPase of guanine-nucleotide-binding proteins in membranes of undifferentiated HL-60 cells. In Pam3CysSer(Lys)4-differentiated HL-60 cells, the responsiveness to the [Ca2+]i-increasing agonists, N-formyl-L-methionyl-L-leucyl-L-phenylalanine, C5a and leukotriene B4, was increased, whilst the responsiveness to prostaglandin E1 and isoproterenol was decreased. Pam3CysSer(Lys)4 did not inhibit proliferation of HL-60 cells but decreased transferrin receptor expression and increased C3bi receptor expression. Pertussis toxin did not affect proliferation and expression of transferrin and C3bi receptors. Dibutyryl cAMP was considerably more effective than Pam3CysSer(Lys)4 at inducing alterations in the above parameters. Our results suggest that (a) Pam3CysSer(Lys)4 induces incomplete functional differentiation of HL-60 cells through a mechanism which does not depend on a rise in [Ca2+]i and is different from that of other differentiation-inducing substances and (b) the mechanism by which Pam3CysSer(Lys)4 induces differentiation involves pertussis-toxin-sensitive and pertussis-toxin-insensitive mechanisms.
The density and species prevalence of dust mites were determined at various times over a 5-year-period in 252 homes of dust mite sensitive people with asthma who lived in eight geographic areas of the United States (Cincinnati, Ohio; New Orleans, La.; Memphis, Tenn.; Galveston, Texas; Greenville, N.C.; Delray Beach, Fla.; San Diego and Los Angeles, Calif.). The most common dust mites found in the homes were Dermatophagoides farinae (DF), D. pteronyssinus (DP), Euroglyphus maynei (EM), and Blomia tropicalis. All homes in all locations contained Dermatophagoides spp. mites, but few homes were populated exclusively by either DF or DP alone. Most homes (81.7%) were coinhabitated by both DF and DP. In coinhabited homes one species was predominant and usually made up at least 75% of the total mite population. Prevalence of the dominant or only species present varied between homes within a geographic area. EM occurred in significant numbers in 35.7% of homes in New Orleans, Memphis, Galveston, Delray Beach, and San Diego. Blomia tropicalis occurred in these same cities but in low densities. For all dust samples, only 13 homes of the 252 sampled had 100 or fewer mites/gm dust, which is considered to be the threshold for sensitivity. Most homes had average mite densities of 500 or more mites/gm dust. The results of the present study suggest a significant and widespread occurrence of both DF and DP. Therefore extracts of both mite species should be considered for diagnostic tests and immunotherapy. Significant levels of EM were present in some areas. Thus sensitivity to EM should be considered in these areas.
BACKGROUND: The value of thrombolytic therapy in unstable angina is unclear. METHODS AND RESULTS: To study this problem, 159 patients were studied in a double-blind, placebo-controlled multicenter trial. Patients without a previous myocardial infarction, with a typical history of unstable angina, and ECG abnormalities indicative of ischemia were included. After baseline angiography, study medication (anistreplase or placebo) was given. Angiography was repeated after 12-28 hours. A significant decrease occurred in diameter stenosis between the first and second angiogram in the anistreplase group compared with the placebo group (11% versus 3%, p = 0.008). This difference was caused by reopening of occluded vessels in the thrombolytic group. However, no beneficial clinical effects of thrombolytic treatment were found. Bleeding complications were significantly higher in patients who received thrombolytic therapy (21 versus seven patients, p = 0.001). CONCLUSIONS: Thus, angiographic but no clinical improvement after thrombolytic treatment with anistreplase was found in patients with unstable angina with an excess of bleeding complications. Therefore, thrombolytic treatment cannot be recommended in patients diagnosed as having unstable angina until proven otherwise.
Recent observations have shown that the presumed target antigen of cytoplasmic islet cell antibodies (ICA) has properties of a monosialo-ganglioside migrating between GM2 and GM1 standards (GM2-1) and that ICA binding is higher in nonobese diabetic (NOD) than in C57BL/10SnJ mouse pancreatic frozen sections. This study aimed to characterize the ganglioside expression in NOD mouse islets in comparison with the control C57BL/10SnJ strain, taking into account possible sex differences, variations with age, and changes after autoimmune beta-cell destruction. Thus, acidic glycolipid composition was analyzed 1) in isolated islets from 11-week-old female and male NOD mice and age-matched female and male C57BL/10SnJ mice, and 2) in whole pancreas of both NOD and control mouse strains at different ages (4, 8, and 18 weeks) and of female NOD mice before and after diabetes onset. The acidic glycolipid GM2-1 is expressed in isolated female NOD islets, male NOD islets, and C57BL/10SnJ mouse islets, but quantitative analysis showed an increased amount of GM2-1 in NOD vs. C57BL/10 islets. GM3 is a ganglioside fraction expressed in female and male NOD mice and not in the C57BL/10 strain, whereas GD3 characterizes the C57BL/10 strain islets. GM2-1 is the sole ganglioside fraction in the whole pancreas to clearly decrease with age in the NOD mouse, and diabetes onset in this strain is associated with a significant decrease in the expression of this component as well as of GM3, whereas other pancreatic ganglioside (GD3, GD1a, and GT1b) levels did not significantly decrease; no age-related ganglioside change was observed in the C57BL/10SnJ mouse. Interestingly, the observed increased ICA binding in NOD islets is paralleled by the increased expression of GM2-1 islet ganglioside, and beta-cell destruction in NOD mice is associated with a significant decrease in the amount of this ganglioside in the pancreas.