Preemployment examinations: how useful?

Preemployment examinations: how useful? An article in the March-April 1991 Journal of the American Board of Family Practice noted a lack of consensus among family physicians regarding preemployment testing of workers. Family physicians do not seem to adhere to any explicit or uniform criteria in performing these tests. Previous writers have suggested how these examinations might help both the employer and the worker. The Americans with Disabilities Act, which went into effect 26 July 1992, however, appears to make true preemployment examinations illegal. A review of the Healthline (1975 to 1991) and the MEDLINE (1980 to 1991) data bases using the MeSH headings "physical examination," "personnel management," "occupational medicine," and "personnel selection" yielded 13 articles dealing with the benefit of preemployment examinations to employees or employers. No studies appeared under the text word "preplacement." All of the published articles addressed the protection of the employer in some manner, but only three studies revealed any benefit to the employer or any protective value for the worker. The testing in these three investigations used detailed knowledge of the demands and duties of the job and, therefore, allowed for more task-specific examinations. The paucity of evidence demonstrating the usefulness of preemployment examinations suggests the need for further research and the development of preemployment evaluations that would allow family physicians to examine employees in a consistently beneficial and more standardized manner.


[Lesions of the ureter in obstetric-gynecologic surgery]. The chapter of injuries to the ureter during obstetric-gynaecological surgery continues to be ignored in the literature published over the last decades, in spite of its prevalence in the practice. This has motivated our review and update of this issue. The interest of urological diagnostic procedures prior to surgery and conduit examination at any time during the operation exert some influence on the prevention of this pathology. Preoperative finding and reconstruction lead to better results, which benefit from the use of the urinary route, thus leaving the gut route and self-transplantation for exceptional situations. A new iatrogenic pathology has emerged from the most frequent use of gynaecological endoscopic surgery.


[Renal sarcoma].

[Renal sarcoma]. Among 322 cases of primary malignant renal tumours reviewed between 1969 and 1991, six were renal sarcoma (1.85%). They all presented earlier symptomatology which was not different from other renal tumours, and nephrectomy was performed in all cases, 5 of which died before 14 months. The histopathological diagnose showed two liposarcoma, two carcinosarcomas, all the others being fibrosarcomas.


[Social and family variables related to alcohol consumption]. The present study analyzed some family factors which are considered to be relevant for excessive alcohol consumption. Such analysis is conducted on the data derived from a cross-sectional epidemiological community survey directed to investigate, in a random sample of 1.800 persons of 18 to 65 years of age--and representative of the population of Cantabria--community responses to alcohol consumption. For this we applied among other instruments, a questionnaire designed by the WHO for exploring Alcohol consumption, and which has being extensively used in other countries. We found, among other things, that: i) Among the males excessive alcohol consumption tends to be higher in the single marital status, and also in those with a higher number of brothers; ii) On the females on the contrary, single marital status is associates to higher percentages of non excessive alcohol consumption, while the fact of having a higher number of brothers is related to higher rates of non consumption of alcohol.


[Evaluation of nuclear roundness as a tool for prostatic carcinoma grading]. The microscopic patterns adopted by prostate carcinomas are extraordinarily variable making its histopathological classification and grading extremely complicated. There are numerous systems for prostatic tumours' grading, but many of them lack a truly reproducible character and an acceptable degree of reliability; for this reason, we have studied a series of nuclear microscopic parameters, from a quantitative point of view, in a series of prostatic carcinomas with a minimum follow-up of five years. It was observed that of the morphometric values obtained--area, perimeter, projection on the X- and Y-axis as well as the nuclear roundness factor--the most useful and representative is the latter. Besides, this is an objective parameter to evaluate nuclear anaplasia and can also be considered as a prognostic factor since, in our series, those who died had a greater mean nuclear roundness factor than those who survived.


[The psychiatric emergency in the general hospital: an analysis of the indications for hospitalization]. The following is a study of psychiatric emergencies in a General Hospital in Madrid (Spain). The Psychiatric Emergency Service of the Ramón y Cajal Hospital in Madrid received a total of 3,693 patients in 1988. This was 3.4% of patients seen in the General Emergency Service. The study is based on an analysis of the variables that influence a recommendation of hospitalization and their statistical significance. Hospitalization was recommended more frequently in males and those with diagnoses of depression, alcoholism and schizophrenic or paranoid disorders.


[Detoxification treatment with naltrexone in opiate dependence]. Outcome of a maintenance treatment with naltrexone (350 mg/week) are examined in a sample of 50 patients with opiate dependence disorder. Treatment was followed in an outpatient facility, in a setting similar to patient's own environment. The average attendance rate was of 6.4 months. Six months after the onset of the treatment, 46% of the patients still remained drug-free. Results of treatment was correlated with changes in life style of the addicts. A follow-up study found that, overall, the naltrexone treatment caused an increase in alcohol consumption whereas there was a noticeable decrease in cocaine use. Factors related to successful results were a good work adjustment, no use of other drugs and lack of psychopathology.


[Diagnostic efficacy of echographic urethrography in the study of urethral stenosis. Comparison with radiologic retrograde urethrography]. Presentation of the first study on the diagnostic efficacy in the study of stenosis with ultrasound urethrography (U.U.) as compared to X-ray retrograde urethrography (X.R.U.). Sensitivity of U.U. in anterior bulbar urethra is, in general, higher than that of X.R.U. (100 U.U. > 88 X.R.U.) while X.R.U. specificity is higher in the posterior bulbar urethra (100 X.R.U. > 97 U.U.). In penile urethra both techniques showed a 100% diagnostic efficacy. Stenosis located in the posterior bulbar urethra are the most difficult to diagnose with ultrasound techniques.


[Premorbid adjustment and negative schizophrenic symptoms]. The relationship between premorbid schizoid traits and the positive and negative symptoms assessed by the Andreasen's SANS and SAPS scales was studied in a sample of 115 DSM-III-R schizophrenics. For the assessment of the schizoid traits the abbreviated Philip's scale of premorbid social-personal adjustment was employed. Negative symptoms, excepting the attentional scale, but no positive symptoms were significantly correlated (p < or = .01) with the Philips's scale. These results suggest that the schizoid traits are the behavioral precursors of schizophrenic negative symptoms. The implications of the results for the genetic and vulnerability/stress models of schizophrenia are discussed.


[Extrinsic stenosis of the ureter. Our caseload and review of the literature]. Obstructive uropathy is the common presentation course for various processes with an origin either intraluminar, parietal or extraluminar. A retrospective analysis of 41 cases of extrinsically originated obstructive uropathy seen in our Urology Unit from 1976 to 1991 was carried out. The cases were divided in three groups following an exclusively etiological criterion: 21.9% (9 patients) corresponded to primary retroperitoneal fibrosis; 51.2% (21 patients) to tumoral ureteral obstruction; and 26.8% (11 patients) to non-tumoral processes. For each division established, the features of clinical presentation, performance of the various diagnostic procedures used, and different therapy approaches are described also including a review on the current literature.


[Skin metastasis in prostatic adenocarcinoma]. Skin metastasis of prostatic carcinoma are extremely rare. Presentation of one significant case of these spread.


[Retrovesical hydatid cyst. A new case]. Presentation of one case of retrovesical hydatidic cyst with no evidence of hydatidosis in other abdominal organ. Both the case and the medical-surgical procedures performed are described.


[Pelvic melanoma].

[Pelvic melanoma]. Report of a patient diagnosed with having a pelvian mass which histologically was a melanoma. Discussion of the possible causes of retrovesical mass and treatment of the melanoma.


[Priapism caused by cauda equina compression. Report of a case and review of the literature]. As a result from the mechanical irritation provoked on the sacral roots, the cauda equina compression syndrome can involve, as part of its symptomatic state, involuntary erections and mictional disorders which arise when standing and stretching the spine. In the eight cases of priapism from this cause reported in the international literature, surgical decompression has solved the clinical picture. We now present a new case with the peculiarity that, following unsuccessful surgical therapy, the infiltration of the compromised spinal roots has rendered excellent results.


[Embryonal development of interstitial Leydig cells in the rat testis]. Blood testosterone concentrations are not constant throughout life, there being a direct correlation with the numbers of cells producing that hormone, for which reason the existence of two Leydig's cells populations has been proposed: one foetal formation, which disappears just prior or immediately after birth, and a subsequent adult generation. In recent studies, however, that withdrawal has not been observed. Considering all the above, we have studied the evolution of these elements during the rat foetal period. From a morphological point of view Leydig's cells do not differentiate from those in the gonadal interstice until day 17 of pregnancy, showing a considerable increase in their numbers by day 21: while from that day onwards their numbers decrease they never disappear completely. We believe those cells become differentiated from the interstitial mesenchymal cells, and that their increase is facilitated by the proliferation of these same elements.


On the mechanism of rat uterus desensitization to kallikrein. An inactive form of kallikrein prepared by iodination with cold iodine, did not show any enzymatic or oxytocic action. However, a competitive pattern between this inactive and active kallikrein was observed in rat uterus preparation: When the inactive form was applied several times in the muscle, a single dose of active kallikrein was unable to cause contraction, but a double dose elicited a response. The rhythmic movement caused by a singular dose of active kallikrein, had its time curtailed by adding the inactive kallikrein to the bath. The inactive kallikrein did not interfere with bradykinin activity.


Synthetic substrates and inhibitors for serine proteases from lymphocytes, mast cells, semen, and blood. The substrate specificity of several serine proteases from cytotoxic T lymphocytes, natural killer cells, mast cells, seminal fluid, and blood plasma has been determined with synthetic peptide thiobenzyl ester and p-nitroanilide substrates. Several new enzymatic activities have been discovered. A variety of inhibitors such as isocoumarins, trifluoromethyl ketones, and peptide chloromethyl ketones were used to study these enzymes and were found to be potent inhibitors.


Absorption studies with porcine pancreatic kallikrein in man. Porcine pancreatic kallikrein (PPK), the main component of Padutin (Bayropharm, FRG), is used since 1974 for the treatment of some forms of idiopathic infertility in man. During kallikrein therapy the number of spermatozoa increases, and qualitative and quantitative sperm motility is improved. In order to investigate the intestinal absorption of PPK in man a clinical study with 7 healthy volunteers was performed. 4500 KE (corresp. to 2.8 mg PPK) and 600 KE (corresp. to 0.38 mg PPK) of kallikrein respectively was orally administered in one dosis. Serum and urine samples were collected several times within 24 hours. Seminal plasma was collected 4-5 days before and 8 hours after treatment with kallikrein. Absorbed PPK was determined using a highly sensitive bioluminescence-enhanced enzyme immunoassay (1) and a newly developed light measuring equipment (MTP reader) (3). The limit of detection was 1 pg/ml in serum corresponding to 6 amol PPK per assay. For both groups (600 KE and 4500 KE) absorption of PPK in serum was found. Maximum absorption was observed between 4 and 12 h and between 2 and 6h, respectively, after oral application of kallikrein. Renal excretion plays no important role in the elimination of PPK from serum. In gel filtration experiments with blood samples of volunteers in which absorbed PPK was detected, one peak of immunochemically active material corresponding to a molecular mass of 82 kDa was found. According to our results, kallikrein is absorbed in unaltered form by the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)


Tissue kallikrein clearance by the liver--effect of plasma components on kallikrein uptake by cultured rat hepatocytes. Rat urinary kallikrein (RUK) injected intravenously to the rat rapidly disappeared from the blood circulation and mainly distributed to the liver. RUK was also incorporated to the primary cultured rat hepatocytes. The amounts of RUK incorporated into the hepatocytes increased by preincubation of RUK with rat plasma. These results and SDS-PAGE analysis suggested some plasma components may be involved in tissue kallikrein clearance in the blood.


Tissue kallikrein and the effect of bromocriptine in human prolactin and growth hormone-secreting pituitary adenomas. Tissue kallikrein (TK) is present and co-localises with prolactin producing cells in human prolactinoma and mixed growth hormone (GH) and prolactin-secreting pituitary adenomas. TK immunoreactivity was reduced or absent in these types of adenomas from patients who had received the dopamine agonist, bromocriptine before surgery. Pure GH secreting adenomas had no TK immunoreactivity.


Immunomodulators, inflammation and lysosomal proteinases of macrophages. Zymosan-induced stimulation of mononuclear phagocyte system was used as a model for study of inflammation in vivo. Zymosan administration to mice was followed by increase of macrophage enzyme markers beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase activity in liver and serum. Serum acid glucosidases secretion occurred both after macrophage stimulation by zymosan and macrophage depression induced by GdCl3. Liver granulomatous inflammation resulted increased activity of liver cathepsin B and cathepsin L. There was no changes of cysteine proteinases studied in the case of macrophage depression by GdCl3. The role of lysosomal enzymes secretion in macrophage stimulation and inflammation was discussed.


Alpha 1-proteinase inhibitor and resistance to acute blood loss during injection of beta-1,3-carboxymethylglucan. The present study was undertaken to evaluate the mechanism of protective effect of semisoluble alpha-1,3-carboxymethylglucan during massive acute hemorrhage. CBA mice were injected i.v. with glucan (25 mg/kg) 24 h prior to hemorrhage (50% of blood circulating volume). Survival data indicated that glucan increased survival compared with the control. However alpha 1-proteinase inhibitor activity in serum has been even decreased 24 h after glucan administration. Moreover enhancement of active oxygen form production and leakage of cytosolic and lysosomal enzymes after alpha-1,3-carboxymethylglucan application was noted.


Protein proteinase inhibitor therapy in experimental pancreatitis: pharmacological characterization of the inhibitor. The pharmacodynamical properties of the duck ovomucoid and its effect on the development of experimental pancreatitis in rats have been studied. It has been shown that after intravenous injection the ovomucoid initially accumulated in the liver, kidneys and blood, while after intraperitoneal injection--mainly in the pancreas and kidneys. The inhibitor is removed from circulation by renal filtration, one-half of the injected protein being removed for 4 hr. For the treatment of experimental pancreatitis two modes of ovomucoid administration were used: intravenous and combined (intravenous/intraperitoneal). The ovomucoid intravenous injection in a dose of 16,300 ATU/kg/24 hr resulted in decrease of both the trypsin-like activity and the level of the trypsinogen activation peptide in the blood to the level in intact rats and also in reduction of the primary pancreas destruction. The same effect observed in the case of the ovomucoid combined injection, but with a lower intravenous dose.


The contact activation proteins: a structure/function overview. In recent years, extensive knowledge has been obtained on the structure/function relationships of blood coagulation proteins. In this overview, we present recent developments on the structure/function relationships of the contact activation proteins: factor XII, high molecular weight kininogen, prekallikrein, and factor XI, with the emphasis on the localization of domains on these proteins that are involved in the interaction with activators, substrates and cofactors.


Factors affecting the rate of contact activation in human plasma. The rate of high molecular weight kininogen cleavage in human plasma treated with dextran sulfate depends largely on the length of preincubation at 37 degrees C and the sample size during preincubation. The longer the preincubation with aliquots < 100 microliters, the more refractory to contact activation the plasma became. This effect is not due to prekallikrein or factor XII consumption/inhibition since both proteins are functional in clotting assays and detectable in immunoblots even after prolonged incubation times at 37 degrees C.


Purification of factor XI and some properties of activated factor XI from porcine plasma. Porcine Factor (F.) XI was purified by following three successive chromatographies. By this procedure, about 5.5 mg of F. XI was obtained from 500 ml of the plasma. The F. XI forms dimer, and is heterogeneous molecule, judging from SDS-polyacrylamide gel electrophoresis. The properties of isolated porcine F. XIa are great similar with those of bovine F. XIa.


Human plasma kallikrein processing: proteolysis as an alternative control. Human plasma kallikrein (HuPK) was detected in normal non-activated and dilution-activated plasma by immunoblotting, using polyclonal antibodies. In non-activated plasma, the predominatly detected protein corresponds to prokallikrein (Mr 80,000-90,000). Activated plasma, besides kallikrein, contains larger proteins (Mr > 130,000) that possibly represent complexes between kallikrein and proteinase inhibitors. Plasma also contains species (Mr 43,000) which corresponds to kallikrein heavy chain. In activated plasma, monoclonal antibodies against kallikrein heavy chain detected, besides these same bands described above, two additional bands (Mr 30,000 and 20,000) possibly correspondent to fragments of kallikrein heavy chain.


Chloramine T impairs the receptor-mediated endocytosis of plasma kallikrein by the liver. Treatment of rat plasma-kallikrein with chloramine T (which does not affect neither its amidolytic activity nor its Mr) impairs the hepatic clearance of the enzyme in a dose-related manner. Preperfusion of the liver with chloramine T before the addition of plasma-kallikrein also diminishes the hepatic clearance of the enzyme.


Contact system dependent fibrinolytic activity in vivo: observations in healthy subjects and factor XII deficient patients. The contribution of activation of the contact system to activation of the fibrinolytic system in vivo was investigated in healthy volunteers and in factor XII deficient patients. The plasminogen activating activity in normal plasma was only partially blocked (for 77%) with specific antibodies to tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). The residual activity could be quenched by a monoclonal antibody that inhibits factor XII activity and was not present in patients with a factor XII deficiency. The formation of plasmin upon the DDAVP stimulus as reflected by circulating plasmin-alpha 2-antiplasmin (PAP) complexes was lower in factor XII deficient patients than in healthy volunteers. These results indicate that in vivo the plasminogen activating activity is partially dependent on activation of the contact system. This fibrinolytic activity is impaired in factor XII deficient patients which may explain the occurrence of thromboembolic complications in these patients.


Influence of diabetes mellitus on renal vascular responses to bradykinin. Streptozotocin-induced diabetes resulted in diminished vasodilator responses to bradykinin in the preconstricted isolated perfused kidney of the rat which were associated with decreased renal phospholipase A2 activity and reduced release of PGE2 into the renal venous effluent.


Procoagulant changes induced by oral contraceptives are balanced by an increased fibrinolytic tendency. Oral contraceptives caused increased fibrinogen, FVII, FX, and fibrinolysis. The latter was associated with elevated FXII and PKK, while C1-INH was decreased, ATIII and alpha 2M were unchanged; it could not be accounted for by changes in t-PA, u-PA, PAI, plasminogen, alpha 2-AP, proteins C or S. HCII and alpha 1-PI were increased and may regulate the availability of thrombin and FXIa. The increased FXII/PKK dependent fibrinolytic potential and HCII may offset any increase in thrombin generation, while alpha 1-PI limits intrinsic coagulation.


Studies on blood coagulation-fibrinolysis system regarding kallikrein-kinin system in the utero-placental circulation during normal pregnancy, labor and puerperium. In our previous study (Adv. Exp. Med & Biol., 247B. 569. 1989, 198B. 41. 1986, blood & vessel, 17: 51. 1986), we reported on the mechanism of coagulation-fibrinolysis system and kallikrein-kinin system in the utero-placental circulation during normal pregnancy, labor and puerperium. The samples were collected from the uterine artery (UA), uterine vein (UV) and peripheral vein (PV). In this study, we tried to elucidate the mechanism of coagulation-fibrinolysis with relation to kks by measuring of Thrombin/Antithrombin III complex (TAT), tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI) complex (tPA.PAI.C), active plasminogen activator inhibitor 1 (active PAI), alpha 2-plasmin inhibitor/plasmin complex (PIC). In 20 normal pregnant women, the levels of TAT, tPA.PAI.C and active PAI significantly increased the first trimester (TAT 4.31 +/- 2.05 ng/ml, tPA.PAI.C 39.52 +/- 17.34 ng/ml, active PAI 39.58 +/- 15.29 ng/ml, n = 20 M +/- SD P < 0.001) to the third trimester (TAT 6.39 +/- 1.93 ng/ml, tPA.PAI.C 57.94 +/- 30.80 ng/ml, active PAI 304.24 +/- 148.64 ng/ml, n = 20 M +/- SD P < 0.001) as compared with those of non-pregnant women (TAT 1.60 +/- 0.89 ng/mg, tPA.PAI.C 11.72 +/- 4.59 ng/ml, active PAI 11.53 +/- 7.48 ng/ml, n = 16 M +/- SD). In utero-placental circulation, the levels of TAT significantly increased (TAT 22.12 +/- 20.03 ng/ml n = 20 M +/- SD P < 0.001) in UV, and tPA.PAI.C and PIC. markedly increased (tPA.PAI.C 93.38 +/- 56.05 ng/ml, PIC 1.03 +/- 0.94 micrograms/ml n = 20 M +/- SD P < 0.02) in UV, but active PAI markedly decreased (active PAI 244.18 +/- 87.55 ng/ml n = 20 M +/- SD P < 0.02) as compared with those in PV (TAT 6.1 +/- 2.09 ng/ml, tPA.PAI.C 59.34 +/- 18.99 ng/ml, PIC 0.49 +/- 0.24 micrograms/ml, active PAI 349.14 +/- 157.34 ng/ml, n = 20 M +/- SD). These findings suggest that the significant increase in those complexes in UA has produced a deposition of fibrin clots in the area in contact with utero-placental blood vessel, although the marked increase in tPA.PAI.C and PIC incompletely inhibited the fibrinolytic activity of tPA by the active PAI. The kks shows a consumption of prekallikrein, LMW-kininogen and HMW-kininogen, and an overproduction of kinin in UV.


Studies of blood coagulation-fibrinolysis regarding kallikrein-kinin system in severe preeclampsia. In our previous study 1), 2), 3) we reported the changes of coagulation-fibrinolysis, kallikrein-kinin system and kininase in preclampsis. In this study, we tried to obtain systemic information of chronic DIC status with regard to kallikrein-kinin system in severe preeclampsia. This systemic information was evaluated in 20 cases of normal gravidas from 28 to 42 weeks of gestation as a control by measuring plasma Thrombin/Antithrombin III complex (TAT), tissue plasminogen activator (tPA) plasminogen activator inhibitor (PAI) complex, active plasminogen inhibitor-1 (active PAI), 2PI plasmin complex (PIC). The levels of plasma TAT and tPA significantly increased (TAT = 10.9 +/- 8.3 ng/ml n = 24 M +/- SD P < 0.02, tPA = 6.1 +/- 3.2 ng/ml n = 10 M +/- SD P < 0.01), tPA PAI C and active PAI markedly increased (tPA PAI C = 85.07 +/- 50.01 ng/ml n = 24 P < 0.05, active PAI = 407.4 +/- 166.0 ng/ml n = 24 P < 0.205), and PIC and D-dimer = 435.1 +/- 145.2 ng/ml n = 8 M +/- SD P < 0.001) in severe preeclampsia as compared with those of normal values (TAT = 6.1 2.0 ng/ml, tPA = 3.6 +/- 1.5 ng/ml, tPA PAI C = 57.9 +/- 30.8 ng/ml, active PAI = 304.2 +/- 148.6 ng/ml, PIC = 0.49 +/- 0.24 mg/ml, D-dimer = 282.9 +/- 75.3 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)


Bradykinin-mediated metabolic effects in isolated perfused rat hearts. Bradykinin perfusion (BK 1 x 10(-12) to 1 x 10(-8) mol/l) of isolated working rat hearts with postischemic reperfusion arrhythmias induced a reduction of the incidence as well as duration of ventricular fibrillation, improvement of cardiodynamics via increased left ventricular pressure, contractility, and coronary flow without changes in heart rate. These beneficial effects were accompanied by reduced activities of the cytosolic enzymes lactate dehydrogenase and creatine kinase as well as lactate output. In the myocardial tissue lactate content was reduced and the energy rich phosphates increased compared to saline perfused control hearts. Glycogen stores were also preserved. These beneficial effects of BK were concentration-dependently abolished by perfusion of the B2 kinin receptor antagonist HOE 140 and the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA). These results suggest that improved cardiac function during and after myocardial ischemia as well as increased energy rich phophates and glycogen stores are mediated by BK and the subsequent release of NO, shifting myocardial metabolism during ischemia and reperfusion to the glucose pathway which leads to changes indicative for cardioprotection.


Evidence that nitric oxide or a related substance is a neurovasodilator in the submandibular gland of the cat. Close-arterial injection of L-NG-nitro arginine methyl ester, a compound that inhibits the synthesis of nitric oxide (NO), caused a dose-dependent reduction in both the parasympathetic and sympathetic (rebound) nerve-induced vasodilatation within the submandibular gland of the cat. At the same time, salivary secretion produced by each nerve was relatively unaffected, and the sympathetic vasoconstriction was enhanced. These results suggest that NO or a related compound may be either a neurotransmitter or neuromodulator contributing to the autonomic nerve-induced vasodilatation in the submandibular gland of the cat.


Increased sensitivity of guinea pig gallbladder in vitro to bradykinin. Bradykinin evoked concentration dependent contractions of guinea pig gallbladder smooth muscle strips in vitro. Responses to kinins increase over three hours of incubation. Induction of a B1-mediated action, waning activity of endogenous kininase(s) and involvement of eicosanoids as mediators have been investigated as potential contributing mechanisms to the four-fold, time dependent increase in response of this tissue to bradykinin.


Involvement of bradykinin-induced [Ca2+]i oscillations in phosphatidylcholine breakdown in K-ras-transformed fibroblasts. Bradykinin (BK) induced a biphasic 1,2-diacylglycerol production in both K-ras-transformed (DT) cells and its parent NIH3T3 cells. The first phase was coincident with the transient phosphoinositide turnover and the second sustained phase was derived from hydrolysis of phosphatidylcholine (PC). In DT cells, the PC breakdown was considerably due to phospholipase C and dependent on intracellular calcium oscillations.


Renal alteration and development of hypertension in diabetic rats. There is a close association between diabetes and hypertension. Many studies have demonstrated an increased incidence of hypertension in the presence of diabetic nephropathy. The aim of the present work was to study the kallikrein-kinin system during the diabetic states with hypertension. In this study neonatal rats were injected with streptozotocin at two days of age. Plasma glucose, proteinuria, urinary kallikrein, blood pressure, creatinine clearance, diuresis and body weight were measured. control rats vs diabetic rats. Plasma glucose (mg/dl): 0 minutes 80.2 +/- 2.5 vs 105.5 +/- 4.5; 60 minutes 120.4 +/- 2.3 vs 220.0 +/- 4.6; 120 minutes 105.0 +/- 1.5 vs 140.0 +/- 3.6; p < 0.05. Proteinuria at 8 months of age (mg/24 hs): 12.5 +/- 1.6 vs 20.6 +/- 2.4; p < 0.05. Urinary kallikrein at 8 months of age (umol/min/24 hs)/(ml/min) x 10(3): 46.9 +/- 3.0 vs 28.5 +/- 2.5; p 0.005. Blood pressure at 8 months of age (mm Hg): 110.0 +/- 2.0 vs 132.0 +/- 4.0; p < 0.001. Creatinine clearance at 10 months of age (ml/min): 0.46 +/- 0.03 vs 0.70 +/- 0.14; p < 0.05. Diuresis at 8 months of age (ml/24 hs): 1.55 +/- 0.65 vs 10.30 +/- 1.44, p < 0.001. The early modifications of kallikrein-kinin system in the diabetes states may contribute to development hypertension with modifications in the hemodynamics renal function.


Isolation of a thiol-dependent acid kininogenase from rat spleen. The enzyme which could produce kinin-like peptides from rat plasma at acidic condition and at coexistence of thiol compound was separated from acid extract of rat spleen. The isolation procedure of this enzyme was established. Substrate specificity was examined against fluologenic substrates and two types of collagen. The purified enzyme was proved to have kinin-forming activity and also collagenlytic activity.


Cell membrane potential oscillations induced by kinins in fibroblasts expressing the Ha-ras oncogene. In NIH-3T3 fibroblasts expressing the ras oncogene (+ras) bradykinin (BK) elicits sustained oscillations (1/min) of cell membrane potential (PD) due to oscillations of intracellular calcium activity with subsequent activation of calcium sensitive K+ channels. In NIH-3T3 fibroblasts not expressing the oncogene (-ras), BK leads to a single transient hyperpolarization of the cell membrane, not followed by oscillations. The oscillations of cell membrane potential require the presence of extracellular calcium and are abolished by K+ channel blocker barium (1 mmol/l), as well as by calcium channel blockers cadmium (1 mmol/l), lanthanum (0.1 mmol/l) and nifedipine (10 mumol/l). However, the oscillations are not modified by 1 mumol/l nifedipine, or by other calcium channel blockers, such as verapamil (10 mumol/l) or diltiazem (10 mumol/l). Cell proliferation is inhibited by nifedipine (10 mumol/l) but not by verapamil or diltiazem, indicating that the oscillations of intracellular calcium are a prerequisite for the growth factor independent proliferation of ras oncogene expressing cells.


Regulation of bradykinin-induced chloride secretion in a human epithelial cell line. The chloride secretory response to bradykinin in T84 cells is regulated. The efflux rate of 125I from these cells can be used to measure this response, and to demonstrate that the sensitivity to bradykinin varies with time in culture. The response in NuT84 cells is greater than that in T84, and can be blocked by the B2 receptor antagonist HOE-140.


Desensitization of bradykinin-induced activation of peripheral nociceptors. Bradykinin-induced activation of peripheral nociceptors has been studied in an isolated spinal cord/tail preparation from the neonatal rat. Prolonged administration of bradykinin consistently produced a selective desensitization which could be prevented by concanavalin A but not by succinyl concanavalin A or phenylarsine oxide. These data indicate that mannose-containing glycoproteins occur in or close to the bradykinin receptor site. In addition the desensitization observed under the present conditions, did not involve the internalization of bradykinin receptors.


The kallikrein--kinin system in blood vessels. We have previously reported that vascular tissue contains kallikrein and kallikrein mRNA. We can now show that kallikrein is present throughout the vascular tree and is released from arterial and venous rings incubated "in vitro". Using the isolated perfused rat hindquarters as a model, we found that kallikrein appeared in the perfusate in concentrations that increased linearly with time. Treatment with puromycin inhibited kallikrein release by 87% (p < 0.01), these data suggest that kallikrein is synthesized and released by the vascular wall. Local generation of kinins (autocrine/paracrine system) may contribute to the regulation of vascular homeostasis.


Vascular wall kininogen concentration is inversely related to intrinsic kininogenase in spontaneously hypertensive rats. We determined kininogen concentration and kininogenase activity in the blood-free, aorta homogenates of 15 week old spontaneously hypertensive rats (SHR) and in their age-matched wistar kyoto (WKY) controls. Active kininogenase in the SHR was only 18% of the WKY controls. Thus, the kininogen concentration was inversely related to kininogenase activity suggesting a local interaction of these components and possible generation of kinins within the vascular wall.


Effects of bradykinin and Des-Arg9-bradykinin on the ischemic rat heart. In isolated rat hearts subjected to 30 min stop flow followed by 5 min reperfusion, Bradykinin (Bk), 1 and 0.1 microM, significantly decreased ventricular tachycardia and fibrillation, noradrenaline (NA) output at reperfusion as well as myocardial NA loss and lipid peroxidation, and preserved creatine kinase activity. Des-Arg9-Bk 0.1 microM had also similar effects. Hence, the active metabolite des-Arg9-Bk may be involved in the protective action of Bk, partly mediated by its inhibitory effect on NA liberation.


The effect of bradykinin on coronary flow and its potentiation by SH-containing ACE-inhibitors. Bradykinin plays a role in the regulation of coronary blood flow. Under basic conditions the vasodilating effect is primarily mediated by stimulation of the endogenous nitrovasodilator endothelium-derived relaxing factor (EDRF). This effect is shortlasting but can be increased and prolonged by sulfhydryl(SH)-containing agents. ACE-inhibitors may cause coronary vasorelaxation by a bradykinin-mediated release of EDRF. This can be potentiated by the presence of SH-groups, as was shown with captopril and zofenoprilat. As a consequence, SH-containing ACE-inhibitors may potentiate nitrates, because they act as exogenous nitrovasodilators, and reverse tolerance to their therapeutic effect.


Direct effects of bradykinin on glomerular filtration and proximal tubule reabsorption in rat kidney. Intrarenal infusion of a low dose of bradykinin devoid of extrarenal action exerts direct vasodilator and diuretic effects on rat kidney. It does not significantly alter glomerular filtration rate and absolute proximal reabsorption but increases the delivery of fluid from the proximal tubule evaluated by the clearance of lithium. None of these effects are observed in kidneys infused with both bradykinin and a specific bradykinin antagonist.


Kallikrein and kinin release using superfused disaggregated cortical cells from rat and human kidney: effects of AVP and dopamine. Potential regulators of the renal Kallikrein-Kinin System are poorly defined. We have therefore examined the effect of arginine vasopressin and dopamine on the release of kallikrein and kinin from collagenase-dispersed rat and human renal cortical cells.


Kinin antagonist blunts the diuretic effect of furosemide in deoxycorticosterone-treated rats. Furosemide at a dose of 3 mg/kg body wt increased urinary volume (vehicle: 12.8 +/- 0.6; furosemide: 42.4 +/- 2.6 ml/8h, p < 0.01) and urinary sodium excretion (vehicle: 0.9 +/- 0.1; furosemide: 5.0 +/- 0.4 mM/8h, p < 0.01) in deoxycorticosterone-treated rats. These effects were associated to a decrease in mean blood pressure (from 122 +/- 4 to 113 +/- 3 mmHg, p < 0.01) and renal vascular resistances (from 15.6 +/- 0.6 to 14.3 +/- 0.7 RU, p < 0.05). The B2-receptor antagonist D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin significantly blunted the diuretic and natriuretic effect of furosemide and completely prevented the decrease in blood pressure and renal vascular resistances. The renal kallikrein-kinin system may modulate the diuretic and hemodynamic effects of furosemide in conditions of increased mineralcorticoid activity.


ACE inhibitor effect on bradykinin metabolism in the vascular wall. In the isolated rabbit thoracic aorta the ACE inhibitor ramiprilat attenuated bradykinin degradation by enzymes localized on vascular endothelial cells as well as on vascular smooth muscle cells by 26% and 32%, respectively. We conclude that the ACE inhibitor can attenuate vascular bradykinin degradation not only by inhibition of endothelial ACE but also by inhibition of other bradykinin degrading enzymes in deeper layers of the vascular wall.


Local production of kinins contributes to the endothelium dependent relaxations evoked by converting enzyme inhibitors in isolated arteries. The angiotensin converting enzyme (ACE) inhibitor perindoprilat evokes endothelium-dependent relaxations in perfused isolated canine arteries. Kininogens, the precursors of bradykinin, elicit endothelium-dependent relaxations which are potentiated by perindoprilat, inhibited by B2-kinin antagonists and partially impaired after inhibition of NO synthase. These observations suggest that locally produced kinins may stimulate the production of NO and endothelium-derived hyperpolarizing factor, and that this action is potentiated by ACE inhibitors.


Captopril as a modifier of the arachidonate cascade of rat platelets. The lipoxygenase pathway of arachidonate cascade in the platelets of spontaneously hypertensive rats has been found to be significantly higher than in normotensive animals. Repeated oral administration of Captopril (in drinking water - 200 mg/100 ml) for 14 days resulted in an elevation in the activity of arachidonate cascade in the platelets of treated rats. At the same time the Captopril treatment induced the formation of 12-hydroxy-heptadecatrienoic acid (12-HHT), which molecule is known to be a potent prostacyclin (PGI2) releaser and/or synthesis inducer. PGI2 is one of the most potent vasodilatator molecule in living organisms. The in vitro experiments in rat platelets suggest, that very low doses of Captopril (10(-12) to 10(-10) M) result in a significantly elevated 12-HHT synthesis. Captopril might act through the 12-HHT--PGI2 mechanism, resulting in blood pressure reduction. The lipoxygenase pathway of platelets, the formation of 12-hydroxyeicosatetraenoic acid (12-HETE), was significantly elevated in vitro in the presence of low dose of Captopril (10(-11) and 10(-10) M).


Cardioprotection of ACE inhibitor in ischemic heart is not dependent on the local angiotensin II formation. Angiotensin II (AII) and bradykinin (BK) release into anterior interventricular vein (AIV) increased significantly 30 minutes after left anterior descending artery (LAD) occlusion in the absence of kidneys. Captopril enhanced BK release, but did not suppress the increase of AII release. Nafamostat suppressed both releases. Infarct size was significantly reduced by captopril but not by nafamostat. These results suggest that cardioprotective effect of captopril might be dependent on local BK accumulation, but not on suppression of local AII generation.


Action of a novel kinin precursor, Met-T-kinin-Leu, on prostaglandin I2 and blood pressure. The novel kinin precursor, Met-T-kinin-Leu, stimulated the release of prostaglandin I2 from endothelial cells cultured using bovine carotid artery endothelial cells and minimum essential medium supplemented with 10% fetal calf serum. However, it failed to stimulate the release of prostaglandin I2 from the cells in the fetal calf serum-free medium conditions. To examine the discrepancy of the release of prostaglandin I2 from the cells by Met-T-kinin-Leu in the presence or absence of fetal calf serum, the products formed from Met-T-kinin-Leu by incubation of culture medium were analyzed by reverse-phase HPLC. Regarding the blood pressure reaction of Met-T-kinin-Leu, it showed from one fifth to one hundredth of that compared with bradykinin in blood pressure reactivity of each species, such as rats, rabbits and cats.


The renal kallikrein-kinin system at the prehypertensive stage of hypertension. In essential hypertension, renal dopaminergic activity and PGE2 was suppressed as was the renal kallikrein-kinin system. The suppression of the renal depressor systems may play an important role in the etiology of hypertension through sodium and body fluid retention. At the prehypertensive stage of essential hypertension, renal dopaminergic activity was suppressed, which induced the retention of body fluids and sodium. On the other hand, the renal prostaglandin E2 was augmented, and it seemed to be a compensatory mechanism for sodium retention. We could not confirm the suppression of the renal kallikrein-kinin system at the prehypertensive stage of hypertension. Although all renal depressor systems are suppressed in essential hypertension, the suppression of the renal kallikrein-kinin system and PGE2 seem to be very important in the etiology of hypertension. Further study is necessary to clarify when both systems are suppressed.


Lack of oral kallikrein in lowering systemic blood pressure in primary hypertension. Primary hypertension is associated with a lack in renal kallikrein activity which might be one of the reasons for the blood pressure elevation. Some smaller and partially uncontrolled studies suggested that an oral substitution of glandular kallikrein lowers blood pressure by a kinin-mediated vasodilation and increased natriuresis. To test this hypothesis we treated in two studies over 100 patients with untreated mild to moderate primary hypertension (WHO I-II) for 5 resp. 12 weeks in a double blind randomized and placebo controlled manner with 1800 U glandular kallikrein orally. Blood pressure measurements were performed according to the two study designs after 3 and 5 resp. 8 and 12 weeks of treatment sphymomanometrically in the day time course. No significant changes in blood pressure by kallikrein treatment could be observed at any time. Neither renal kallikrein excretion, renin and ACE-activity nor blood glucose concentration in diabetics or non-diabetics was changed. Thus, we could undoubtedly demonstrate that oral applied glandular kallikrein has no effect on primary hypertension.


The kallikrein-kinin system in early state of diabetes. The kallikrein-kinin system was studied in 9 normals, healthy subjects (6 men, 3 women, age range 1 to 14 years) and 15 diabetic patients (9 men, 6 women age range 2 to 14 years) with an evolution of the disease between 1 to 14 years. Diabetic patients with low microalbuminuria (6.62 +/- 0.97 mg/24 h) show increased total and pre-kallikrein respect to control (3 and 2 fold respectively). On the other hand patients with high microalbuminuria (44.7 +/- 13.2 mg/24 h) show a total and pre-kallikrein of more than 4 and 8 fold increased respectively, compare with the control. According with these results we can concluded: 1) The total kallikrein and pre-kallikrein is increased in the diabetic state. 2) When microalbuminuria is high, the total and pre-kallikrein correlates with those increasing. 3) These changes could modified the renal hemodynamic in diabetes.


Hageman factor dependent activation and its relationship to lethal Pseudomonas aeruginosa burn wound infections. Trauma causes increases in total protease load in the circulation of the traumatized host animal or patient. This increase is due, in part, to Hageman Factor activation followed by down-line cascade system activation. Concomitant with the activation of these systems is a reduced host capacity to resist infection. Infection superimposed on a traumatized host increases the total host protease load even more by additional activation of Hageman Factor and cascade systems.


Liver and serum lysosomal enzymes activity during zymosan-induced inflammation in mice. Liver and serum lysosomal enzymes (acid glucosidases and cysteine proteinases) during zymosan-induced stimulation of MPS or MPR depression induced by GdCl3 have been studied. Zymosan was used as a model for study of inflammation in vivo. The development of inflammation induced by zymosan was followed by increase activity of macrophage activation markers - beta-N-acetylglucosaminidase (NAGlu) and beta-N-acetylgalactosaminidase (NAGal) in liver and serum. There was enhance of liver cysteine proteinases activity. Similar, less prominent (partly) data were obtained during macrophage depression induced by GdCl3.


Plasma exudation by activated plasma kallikrein after intraperitoneal injection of lambda-carrageenin or endotoxin in rats. The experimental study was carried out to examine whether intraperitoneal injection of carrageenin or endotoxin activates plasma kallikrein-kinin system to induce plasma exudation in rats. Intraperitoneal injection of 2% lambda-carrageenin induced plasma exudation in the peritoneal cavity by activation of plasma prekallikrein. Intraperitoneal injection of endotoxin (3mg/kg) also resulted in intraperitoneal plasma exudation, but plasma kallikrein-kinin system did not seem to be involved.


The role of alpha 1-proteinase inhibitor in semisoluble glucan induced resistance to hemorrhage. The present study was undertaken to evaluate the mechanism of protective effect of semisoluble beta-1,3-carboxymethylglucan (CMG) during acute massive hemorrhage. CBA mice were injected i.v. with glucan (25 mg/kg) 24 h prior to hemorrhage (50% of blood circulating volume). Survival data indicated that glucan increased survival compared with control. However, alpha 1-proteinase inhibitor activity in serum have been even decreased 24 h after glucan administration. Moreover enhancement of active oxygen form production and leakage of cytosol and lysosomal enzymes after CMG application were noted.


Determination of tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complexes in synovial fluid of patients with rheumatoid, osteo and psoriatic arthritis. An enzyme-linked immunosorbant assay was developed to determine tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complexes in pooled synovial fluid of patients with rheumatoid, osteo and psoriatic arthritis. Even though basal values could be determined, the addition of synovial fluid shifted the standard curves for both tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complex to the right, because of the presence of a novel inhibitor.


Comparison of plasma prekallikrein levels in human skin blister and chamber fluids from volunteer subjects and psoriatic patients. Suction blisters were successfully raised on lesional, perilesional and non-lesional skin of psoriatic patients. Similar blisters were created on the skin of volunteer subjects. A specific method has been established for the measurement of plasma prekallikrein, and validated for blister fluid, skin chamber fluid, plasma and synovial fluid. Combined levels of plasma prekallikrein and its active form were compared in blister fluids obtained from psoriatic patients and the volunteers. Significantly higher values for plasma prekallikrein were found in the non-lesional blister fluids of psoriatic patients when compared to the volunteer subjects.


Changes in polymorphonuclear neutrophil-elastase in pancreatitis. In cases of acute and chronic pancreatitis, we measured the amount of polymorphonuclear neutrophil (PMN)-elastase. There was a significantly larger increase in PMN-elastase in patients with pancreatitis than normal adults. Especially, there was a particularly notable increase in amount of PMN-elastase in patients with severe pancreatitis. Furthermore, the peak of PMN-elastase increase throughout the course of the pancreatitis was seen to be 1-2 days after peak increase in pancreatic enzymes. In the experiment in which pancreatic juice and pig pancreatic kallikrein were added to granulocytes in vitro, we recognized a gradual release of PMN-elastase. From these data, we suggested that timely measurements of PMN-elastase are useful to marker of monitoring clinical changes in severe pancreatitis.


CP-0127, a novel potent bradykinin antagonist, increases survival in rat and rabbit models of endotoxin shock. The bradykinin antagonist dimer CP-0127 was found to be a potent and selective inhibitor of the depressor response to bradykinin in the anaesthetized rat and rabbit. When given as a single dose s.c. (3.6 mumol/kg), the depressor response to bradykinin was blocked for the duration of the experiment (4 hours). In anaesthetized control rats, LPS from E. coli produced a profound and immediate hypotensive response, while in rats infused with CP-0127, the response to LPS was almost totally reversed. In addition, CP-0127 given as a single subcutaneous dose (3.6 mumol/kg) to rats 1 hour before LPS challenge produced a 93% survival rate, compared to 14% in control animals. Finally, a survival rate of 86% was achieved in rabbits infused with CP-0127 at 0.36 nmol/kg/min i.v., compared to 45.5% in saline-infused control animals given LPS (500 micrograms/kg i.v.). The results of these experiments provide evidence for a significant role for the kallikrein-kinin system in these models of endotoxic shock, and indicate the therapeutic potential of a bradykinin antagonist such as CP-0127 for treating this disorder in man.


The bradykinin antagonist Hoe 140 inhibits carrageenan- and thermically induced paw oedema in rats. The new and highly potent B2 bradykinin (BK) antagonist Hoe 140 was tested for its ability to inhibit oedema of rat paws induced by scalding and carrageenan. The data show that Hoe 140 inhibits scalding and carrageenan oedema for more than four and six hours, respectively. Based on its potency against actions of endogenously generated kinins Hoe 140 is appropriate to investigate the role of kinins in human inflammatory diseases.


Effect of bradykinin on airway function. Bradykinin (BK) has several effects on airway function which may be relevant in obstructive airways disease. These effects are mediated via B2-receptors. BK is a potent bronchoconstrictor in animals and humans in vivo. Bradykinin contracts airway smooth muscle, is a potent bronchial vasodilator, increases microvascular leakage, stimulates epithelial cells to release bronchodilators and stimulates mucus secretion. Perhaps its most important action is the activation of sensory nerves in airways, leading to reflex bronchoconstriction, coughing and neurogenic inflammation through the release of neuropeptides from sensory nerves.


The potential role of bradykinin antagonists in the treatment of asthma. The potential role of bradykinin and the use of bradykinin antagonists in the treatment of allergic airway disease (asthma) was studied by determining the effects of the bradykinin B2 receptor antagonist, NPC-567 (D-Arg-[Hyp3,D-Phe7]-bradykinin) on antigen-induced early and late bronchial responses, airway inflammation, mediator release and airway hyperresponsiveness in the sheep model of allergic asthma. In the control trial, antigen challenge produced an early bronchoconstrictor response that was associated with an increase in immunoreactive-kinins in bronchoalveolar lavage fluid (BAL), and a late bronchial response that was associated with increased concentrations of leukotriene [LT]B4 and LTC4 and inflammatory cells (neutrophils and eosinophils) in the BAL. Aerosol NPC-567 given before, during and 4 h after antigen challenge had no protective effect on the early bronchoconstrictor response, but significantly inhibited the late bronchial response. This inhibition was correlated with a reduction in the inflammatory lipid mediators and inflammatory cells in BAL. These results suggest that antigen-induced kinin generation may be important for controlling the release of arachidonic acid metabolites from inflammatory cells that contribute to the development of late responses and airway hyperresponsiveness.


Kallikrein-like activity in the bronchoalveolar lavage (BAL) fluid of sensitized, challenged guinea-pigs. Sensitization and challenge of guinea-pig airways with aerosols of ovalbumin solution administered through an endotracheal tube leads to a significant increase in kallikrein-like enzyme activity in bronchoalveolar lavage (BAL) fluid. This increase is present up to six hours after challenge and may be related to changes in airways resistance that persist for similar periods.


Increase in the kinin levels in the bronchial washings after intravenous injection of leukotriene C4 in guinea pigs. In guinea pig plasma, bradykinin (BK) was degraded mainly to des-Arg1-BK by an aminopeptidase-like enzyme, which was inhibited by 2-mercaptoethanol. Besides this degradation, BK was also hydrolyzed by kininase I and kininase II from C-terminal end to des-Arg9-BK, des-Phe8-Arg9-BK and Arg-Pro-Pro-Gly-Phe ([1-5] BK). The formation of des-9-BK was strongly blocked by DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGPA) and that of des-8,9-BK and [1-5] BK was inhibited by captopril. When guinea pigs were pretreated with a cocktail of 2-mercaptoethanol, MGPA and captopril, intravenous administration of leukotriene (LT) C4 (10 nmol/kg) caused an increase in the levels of free kinin in the bronchial washings of guinea pigs. This increase was accompanied with the increase in glandular-kallikrein activity, which could be inhibited by aprotinin. As BK is reported to induce both bronchoconstriction and bronchial secretion, the increased free BK induced by LTC4 might enhance the effect of LTC4.


Bradykinin and other inflammatory mediators in BAL-fluid from patients with active pulmonary inflammation. We evaluated the levels of bradykinin, albumin, TAME-esterase activity, histamine, PGD2 and LTC4 in bronchoalveolar lavage fluid from asthmatics and from patients with pneumonia, sarcoidosis, fibrosis, and chronic bronchitis. Compared with the results of healthy volunteers and atopic asymptomatic asthmatics the bradykinin levels and TAME-esterase activity were significantly elevated. In all other groups, histamine was additionally elevated in asymptomatic asthmatics, whereas albumin was elevated in symptomatic asthmatics and fibrosis patients, and decreased in chronic bronchitis and pneumonia patients. Following local intrabronchial allergen challenge of mild grass pollen asthmatics out of season bradykinin levels increased significantly, correlated with albumin, histamine and TAME-esterase activity. In contrast to the increased mediator concentrations in the early phase reaction there was no change of BAL cells in asthmatics compared to baseline and healthy volunteers. The presence of bradykinin in the bronchoalveolar space of patients with active pulmonary inflammations and bradykinin generation in asthmatics as a result of intrabronchial allergen challenge provides strong evidence that kinins are involved in inflammatory disorders of the lower airways.


Cough induced by ACE-inhibitors. A kinin related phenomenon? Cough induced by ACE-inhibitors may be related to bronchial hyperreactivity and/or to an accumulation of kinins. In a placebo-controlled, double-blind randomized study in asthmatic and hypertensive patients lung function and bronchial reactivity to histamine and bradykinin remained unaltered although in hypertensive patients with cough, reactivity to histamine tended to be more pronounced and bronchial hyperreactivity to be more frequent than in those without cough. The findings do not support a major role of kinins in ACE inhibitor-induced cough.


The kallikrein-kinin system of sweat in normal and cystic fibrosis subjects. The mechanisms of kallikrein secretion was studied in 25 normal subjects (11 male, 14 female) and 5 subjects with cystic fibrosis (identified by the usual criteria). The results obtained show a decreasing of prekallikrein and total kallikrein in cystic fibrosis stimulated by IPR or pilocarpine compare to controls. On the other hand sweat from males shows more prekallikrein and total kallikrein than females. According with this results we can concluded that the basic defect in sweat cystic fibrosis gland could be the possible involvement of the kallikrein-kinin system on the high osmolality of the sweat secretion.


Modulation of presynaptic sympathetic activity by kinins and related compounds: influence of converting enzyme inhibition. Since converting enzyme and kininase II are identical enzymes and probably influences both, the biosynthesis of Ang II and the metabolism of bradykinin we investigated the effects of bradykinin, desArg-bradykinin and some bradykinin antagonists (desArg[9]-Leu[8]-bradykinin, HOE S 890307) on the sympathetic outflow of pithed SHR or Brown-Norway-Rats before and after acute or chronic inhibition of the converting enzyme by ramipril. bradykinin increased dose dependently the noradrenaline and adrenaline release in particular when the converting enzyme was inhibited. DesArg-bradykinin caused a dose-dependent increase in adrenaline release only after converting enzyme inhibition. The bradykinin-antagonists led to an increase in adrenaline release during ramipril administration. The weak but significant stimulation of adrenaline release by the bradykinin antagonists after converting enzyme inhibition might be due to unspecific actions on the adrenal medulla possibly induced by histamine release from mast cells.


The kallikrein-kinin system in cardiac tissue. Kallikrein and minute amounts of kininogen have been found in rat cardiac tissue. The mRNA for kallikrein was also determined by the polymerase chain reaction using KK-specific probe. The existence of an intrinsic kallikrein-kinin system in the heart raises the possibility that the enzyme-peptide system is involved in local regulation of cardiac function and metabolism.


Early ACE-inhibition in myocardial infarction. Possible role of bradykinin. Restoration of coronary blood flow in the ischemic myocardium is absolutely needed to prevent irreversible cellular damage but on the other hand may have potentially hazardous consequences. Since thrombolysis during myocardial infarction is designed to salvage a maximal number of myocardial cells threatened by ischemia, a concommitant intervention which reduces cellular damage due to reperfusion will improve the net result of such procedure. The adjunctive use of ACE-inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. This article summarizes the results indicating that ACE-inhibitors do play an important role in cardioprotection in the acute phase of myocardial ischemia followed by reperfusion. Probably, their effect on bradykinin breakdown is at least partly responsible for this effect.


Activation of kinins on myocardial ischemia. In experimental ischemic dog heart with coronary-constriction, no increase of coronary blood flow, Max dP/dt or MVO2 with no change of kinin in arterial blood were exhibited. Following sympathetic nerve stimulation, remarkable increases of kinin in coronary sinus blood were observed with a significant elevation of left ventricular end-diastolic pressure and an augmented production of lactate from the heart as well as an ischemic change of ECG-ST. Infusion of kinin into the left main coronary artery resulted in no change in the mean systemic blood pressure, coronary blood flow, coronary vascular resistance, cardiac function, myocardial metabolism or ECG-ST in the control and coronary-constricted groups. These data suggest that kinin was released significantly from the ischemic heart, however, such a level of kinin has no significant effect on coronary circulation or myocardial metabolism. In ischemia-reperfusion rabbit hearts, no significant influence of the ACE inhibitors, captopril and ramiprilat, were observed. Species differences may be responsible for the beneficial role of ACE inhibitors in the limitation of infarct size in the dog hearts, possessing collateral flow, that are not seen in the rabbit heart with poor collateral flow.


The possible role of bradykinin in the antiischemic activity of ACE-inhibitors. The ACE-inhibitor ramiprilat (40 ng/kg/min) was infused for 6 h into the left coronary artery of anesthetized dogs with ligation of the descending branch of this artery. This route of administration and the low dose were chosen to achieve local cardiac effects without affecting systemic hemodynamics. Ramiprilat significantly reduced infarct-size expressed as percentage of the area at risk. The cardioprotective effect of ramiprilat was mimicked by bradykinin and abolished by coadministration of a bradykinin antagonist. These results strongly suggest that bradykinin plays a role in the cardioprotective effect of the ACE-inhibitor ramiprilat.


Aesthetic maxillo-facial surgery: face lifting and S.M.A.S. The article illustrates the importance of face lifting and S.M.A.S. tightening as an adjunct to the aesthetic aspect of maxillo facial surgery, for instance in combination with extreme mandibular set back or advancement in adults. The theory and basic techniques of the face lifting procedure and the S.M.A.S. tightening technique are described. A clinical example is presented. The indications pre- and postoperative management and complications have been mentioned.


Submental liposuction in maxillo-facial surgery. Liposuction is a relatively recent surgical technique used in body contouring plastic surgery to correct fatty dysharmonies. It is of particular interest to the maxillo-facial surgeon to treat submental fat excess. This relatively easy technique is described, using a few clinical examples. Indications in maxillo-facial surgery are the correction of "double chin" deformity and increased submental fullness after orthognathic surgical procedures as mandibular setback, as well as an adjunct to rhytidectomy.


[Role of arthrography in imaging of the temporomandibular joint in 1992]. In this text we briefly want to discuss the role of the arthrographic examination of the temporomandibular joint for detection of disc pathology. We will mention the normal anatomy and function of the temporomandibular joint, the technique for performing arthrograms and the classification of the most frequent disc pathology. This will be illustrated by some arthrographic examples of anterior disc displacement without reduction, disc perforation, and medial disc displacement. Finally the advantages of arthrography in comparison with other investigation techniques will be discussed.


Bilateral maxillary and mandibular fourth molars. Report of a case. Fourth molar do not occur very frequently. They tend to be unerupted or if they erupt may cause malalignment of the dentition or aesthetic problems. The preferred location is in the maxilla, and they may be normal or rudimentary and located either directly distal or distolingually to the maxillary third molar. Supernumerary molars should probably be extracted only when their presence is responsible for the failure of eruption or malalignment of permanent teeth.


Direct angioplasty versus initial thrombolytic therapy for acute myocardial infarction: long-term follow-up and changes in practice pattern. We retrospectively studied the outcomes of patients with acute myocardial infarction who were treated with either direct angioplasty or thrombolytics followed by angioplasty. Two patient cohorts were analyzed: a previously reported (in regard to short-term follow-up) group of 371 patients who now have long-term follow-up (mean, 3.4 years) of survival and event-free survival and a second group of 202 patients who have been treated since publication of our initial data. Both 1-year and 2-year survival were significantly better (p = 0.01 and 0.02, respectively) in the group that was treated with thrombolytics first. Event-free survival (i.e., no myocardial infarction, coronary artery bypass graft surgery, repeat angioplasty) was better overall (p < 0.01) for the group that was treated with thrombolytics first. The more recently treated group of patients also showed benefit in regard to both survival (p = 0.002) and event-free survival (p < 0.01) over a short-term follow-up period (mean, 39 weeks) for patients who were treated initially with thrombolytics as compared with those who were treated with direct angioplasty. Although the initial cohort was very similar to the treatment groups except for age (mean age for the direct angioplasty group was 62 +/- 12 years vs 57 +/- 11 years for thrombolytics first group, (p = 0.0002), several differences existed in the more recent treatment groups. The patients who were more recently treated with direct angioplasty were older, had lower mean ejection fraction, had more extensive coronary artery disease, and were more likely to have had prior coronary artery bypass grafting.(ABSTRACT TRUNCATED AT 250 WORDS)


Thrombolysis with recombinant human tissue-type plasminogen activator during instability in coronary artery disease: effect on myocardial ischemia and need for coronary revascularization. TRIC Study Group. Two hundred five men, 40 to 70 years of age, admitted to the coronary care unit with unstable coronary artery disease (unstable angina or non-Q wave myocardial infarction), were randomized to double-blind placebo-controlled treatment with an intravenous infusion of recombinant tissue-type plasminogen activator (rTPA), 1 mg/kg body weight (maximum 100 mg) during 4 hours, in addition to aspirin, heparin, and beta-blockade. No severe complications occurred. Myocardial ischemia, defined as myocardial infarction, incapacitating angina despite medication, or signs of ischemia at the exercise test, was reduced by treatment with rTPA compared with placebo both at discharge, 53% compared with 70% (p = 0.02), and at 1 month, 61% compared with 80% (p = 0.005). Signs of myocardial ischemia during the exercise test were reduced at discharge 51.0% compared with 68% (p = 0.03) and at 1 month 48% compared with 62% (p = 0.09). Coronary angiography after 1 month showed no difference in major coronary lesions between the groups, nor was there any reduction in the number of performed coronary revascularization procedures. In conclusion, treatment with rTPA in unstable coronary artery disease in men reduced myocardial ischemia but did not significantly reduce the need for revascularization in long-term follow-up.


Outcome of urgent percutaneous transluminal coronary angioplasty in acute myocardial infarction: comparison of single-vessel versus multivessel coronary artery disease. Despite recent clinical trials of percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction, specific groups of patients that may benefit from adjunctive or alternative therapy have yet to be adequately characterized. The in-hospital outcome of 151 consecutive patients treated for acute myocardial infarction with urgent PTCA of the infarct-related artery was studied to identify a subgroup of patients at high risk. Patients were divided into two groups based on the angiographic presence of either single-vessel (n = 86) or multivessel (n = 65) coronary artery disease. Despite PTCA of only the infarct-related artery and similar baseline clinical characteristics such as age, peak serum creatine kinase concentration, left ventricular ejection fraction, and time from the onset of chest pain to arrival at the hospital, the group with multivessel disease had a lower rate of successful angioplasty (75% vs 92%, p < 0.005), with higher incidences of persistent total occlusion of the infarct-related artery (14% vs 3%, p < 0.02) and procedural complications during PTCA (28% vs 13%, p < or = 0.02), and were more likely to have multiple complications (12% vs 1%, p < 0.004). In addition, the group with multivessel disease had a higher rate of urgent (< or = 24 hours) coronary artery bypass graft surgery (13% vs 2%, p < 0.05) and a trend toward a higher in-hospital mortality rate (6% vs 1%, p < or = 0.17). By stepwise logistic regression, only the presence of single-vessel versus multivessel disease was predictive of PTCA success (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)


Calcitonin gene-related peptide in patients with and without early reperfusion after acute myocardial infarction. Plasma concentrations of calcitonin gene-related peptide (CGRP), a potent regulator of vascular tone, creatine kinase, myoglobin, and cardiac troponin T were assessed in 31 patients with acute myocardial infarction. In patients who had sustained acute myocardial infarctions, maximum CGRP concentrations (median, 3.2 pmol/L; interquartile range, 1.5 to 4.8 pmol/L) were markedly elevated as compared with healthy control subjects (n = 23; median, 1.02 pmol/L; p = 0.02). However, no marked differences in CGRP levels were observed between patients with early reperfusion (n = 19; median, 3.5 pmol/L) and patients without early reperfusion (n = 12; median, 2.6 pmol/L; p = 0.96), as well as between those with congestive heart failure (n = 8; median, 3.9 pmol/L) and those without congestive heart failure (n = 23; median, 3.2 pmol/L; p = 0.62). CGRP did not correlate closely with myocardial protein release or hemodynamic parameters (heart rate and blood pressure) or the occurrence of arrhythmias. Therefore we conclude that elevated peripheral venous CGRP concentrations in patients who have sustained an acute myocardial infarction are independent of successful reperfusion and hemodynamic state. Although the cause of CGRP increase is not yet identified, CGRP may play a role in the regulation of coronary vascular tone in patients after acute myocardial infarction.


Adenosine is an endogenous protectant against stunning during repetitive ischemic episodes in the heart. To investigate whether adenosine receptor blockade alters the response to serial coronary occlusions in the rabbit heart, we measured changes in segment length with ultrasonic dimension gauges placed in the field of a coronary branch. The coronary branch was subjected to four 5-minute occlusions, each separated by 10 minutes of reperfusion. In control hearts, the percentage of segment shortening fell from 15.7% to 9.3% after release of the first occlusion with no further deterioration after each of the subsequent three occlusions. In hearts in which adenosine receptors were blocked with PD 115,199, a potent blocker of both A1 and A2 receptors, segment shortening again recovered to about two thirds of the preischemic value during the reperfusion period after the first occlusion. Each subsequent occlusion, however, resulted in a further deterioration of function to the extent that shortening was less than 20% of the preischemic value during reperfusion after the fourth occlusion. Therefore the first occlusion of a series of four occlusions, while mildly stunning the heart, also preconditions the myocardium against further stunning by subsequent occlusions. Because that protection was when adenosine receptors were blocked, adenosine must play an important role in the mediation of this protective effect.


Inosine--a natural modulator of contractility and myocardial blood flow in the ischemic heart? The energetic role of inosine (INO) remains controversial. The aim of the present study was first to test whether endogenous INO consumption/production correlates with regional myocardial contractile performance and second to test whether locally increased levels of INO influence contractility and blood flow in severely ischemic myocardium. Fentanyl-anesthetized dogs with implanted sonomicrometry crystals and independently perfused left anterior descending coronary arteries were studied. Two relatively load-independent indexes of regional myocardial contractility derived from left ventricular pressure-segment length loops were used: the regional stroke work-end-diastolic segment length relationship (Wr/L(ed)) and the end-systolic pressure-segment length relationship (Plv/L(es)). Very good correlations between myocardial contractile performance (as measured by the slope of the regional Wr/L(ed) relationship) and endogenous INO consumption/production under both nonischemic and ischemic conditions were found. Ischemia severely depressed contractility, significantly shifting rightward the Wr/L(ed) and Plv/L(es) relationships. INO infused into the left anterior descending bypass, in a concentration of 600 to 800 mumol/L, partially restored contractile performance as evidenced by a significant leftward displacement of both relationships. Wr, measured at a common maximum L(ed), increased significantly by 61 +/- 5%. Border-zone collateral flow (microspheres) increased by 35 +/- 7% within the endocardial segments and by 34 +/- 9% in the epicardial segments, but no increase in flow in the ischemic region was measureable. With the current emphasis on recanalization with thrombolytic therapy and considering the apparent safety of INO, this naturally occurring nucleoside might prove to be a useful adjunctive agent in the treatment of acute myocardial ischemia.


Comparison of acute elastic recoil after directional coronary atherectomy versus standard balloon angioplasty. We evaluated intraprocedural "elastic recoil" in 25 patients (22 men and 3 women) undergoing directional coronary atherectomy (DCA) of left anterior descending stenoses, and compared these with 25 temporally-matched (14 men and 11 women) patients having balloon angioplasties (PTCA). Quantitative arteriography was performed using the Coronary Measurement System (Leiden, The Netherlands), with "elastic recoil" defined as the difference in maximum device or balloon size minus residual minimum diameter. In addition, we determined the effects of relative device size, specific anatomic location (proximal/mid artery), lesion length, eccentricity (symmetry index), and dystrophic calcification on acute "recoil" severity after both procedures. Although initial coronary stenoses were similar (minimum stenotic diameter, DCA = 0.59 +/- 0.20 mm versus PTCA = 0.55 +/- 0.23 mm, p = NS), less "elastic recoil" was observed after atherectomy (DCA = 0.83 +/- 0.57 mm versus PTCA = 1.26 +/- 0.56 mm, p < 0.01), and this was confirmed by absolute recoil/maximum device size ratios (DCA = 23.5 +/- 16.0% versus PTCA = 41.6 +/- 13.8%, p < 0.01). Acute "elastic recoil" was also influenced by maximum device size/"normal" coronary artery ratios [(ratio < 0.9, DCA = 0.26 +/- 0.10 mm versus PTCA = 0.84 +/- 0.13 mm, p < 0.01); (ratio 0.9 to 1.1, DCA = 0.69 +/- 0.41 mm versus PTCA 0.75 +/- 0.32 mm, p = NS); (ratio > 1.1, DCA = 1.09 +/- 0.64 mm versus PTCA = 1.59 +/- 0.48 mm, p < 0.05)].(ABSTRACT TRUNCATED AT 250 WORDS)


Percutaneous angioscopic evaluation of luminal changes induced by excimer laser angioplasty. Angioscopy has been shown to provide more detailed information on lesion morphology before and after interventional procedures than angiography. Therefore to evaluate the effects of laser angioplasty, angioscopy was performed in five patients with peripheral or coronary vascular disease who underwent excimer laser angioplasty. The excimer laser was operated at 308 nm, 135 nsec, 25 Hz, and 40 to 60 mjoules/mm2 and was coupled into multifiber wire-guided catheters of 1.4 to 2.0 mm diameter for coronary lesions and into catheters of 2.2 mm diameter for peripheral lesions. There were three coronary (one left anterior descending, one circumflex, one right coronary artery) and two peripheral (one common iliac artery, one superficial femoral artery) lesions. Angioscopy was successfully performed before and after laser ablation without any complications in all five lesions. The characteristics of angioscopic findings after excimer laser angioplasty consisted of flaps, fractures of plaques, and abundant tissue remnants. There was no apparent thermal injury. Recanalized channels were small and irregular. These results indicate that (1) angioscopy is effective and safe for evaluation of lesion morphology after laser angioplasty; (2) laser ablation does not result in thermal injury; and (3) irregular channels after recanalization and abundant tissue remnants may explain the suboptimal results after laser angioplasty.


Angiographic restenosis after successful Wallstent stent implantation: an analysis of risk predictors. Follow-up angiographic study was performed in 86 patients after initially successful Wallstent stent (Medinvent, Lausanne, Switzerland) implantation between April 1986 and October 1990. The stent angiographic restenosis rate was 16% at a mean of 8 months after stenting despite the inclusion of a substantial number of patients at high risk of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Of a total 15 variables analyzed, only suboptimal stent placement was found to be a significant predictor of stent restenosis. Age; gender; baseline New York Heart Association functional class; previous PTCA; indication for stenting; left ventricular ejection fraction; preangioplasty and immediate postangioplasty diameter stenosis severity; stented vessel site, lesional morphology; number, diameter, and length of stents implanted; and the interval between stenting and follow-up angiographic restudy were not significant risk factors of stent restenosis. Our study suggests that intracoronary stent implantation with the Wallstent may be a useful and promising adjunctive option after PTCA, particularly in patients at high risk of restenosis after PTCA. However, because of the significantly enhanced risk of restenosis after suboptimal stent implantation, we strongly recommend the selection and placement of Wallstent stents that adequately cover the entire length of the dilated coronary segment.


Lidocaine to prevent ventricular fibrillation in the prehospital phase of suspected acute myocardial infarction: the North-Norwegian Lidocaine Intervention Trial. The efficacy of lidocaine to prevent ventricular fibrillation during the prehospital phase of suspected acute myocardial infarction was assessed 3 hours after administration in a randomized controlled trial. A total of 204 patients examined within 6 hours after onset of symptoms were included, and acute myocardial infarction was later confirmed in 63% of these. Lidocaine, administered as a 100 mg intravenous bolus dose followed by a 300 mg intramuscular injection, failed to prevent ventricular fibrillation, which was observed in 2 (2.1%) of 96 patients in the lidocaine group and in 3 (3.0%) of 101 patients in the placebo group (p = 0.95; odds ratio 0.7, 95% confidence interval 0.4 to 1.3). In addition, sudden cardiac collapse with unknown heart rhythm was observed in three patients who received lidocaine (3.1%) compared with none in the placebo group (p = 0.23; odds ratio 7.6, 95% confidence interval 2.8 to 22.1). The results of this small study suggest that lidocaine, even when given in a high dose, is ineffective in preventing ventricular fibrillation when administered before hospitalization for suspected acute myocardial infarction. Prophylactic use of lidocaine in this situation may therefore not be warranted or advisable.


Determinants of the hemodynamic consequence to sustained ventricular arrhythmias after a single myocardial infarction. Patients who have sustained ventricular arrhythmias after myocardial infarction present with either a cardiac arrest or with hemodynamically stable sustained ventricular tachycardia. Recent reports have suggested a different electrophysiologic milieu in these two patient groups and a higher incidence of cardiac arrest in patients with a history of more than one myocardial infarction. No studies have examined patients with only a single previous myocardial infarction. To assess the determinants of the hemodynamic consequence of sustained ventricular arrhythmias more than 3 days after a single myocardial infarction, 82 patients who were resuscitated from arrhythmic cardiac arrest (CA group, 40 patients) or who had hemodynamically stable sustained ventricular tachycardia (No CA group, 42 patients) were examined. Patients in both groups had similar global left ventricular ejection fractions (mean +/- SD; 30% +/- 12% vs 27% +/- 12%; p = NS), proportion of patients with anterior wall infarctions as compared with the proportion of patients with inferior wall infarctions (55% vs 50%; p = NS), time from infarction to arrhythmia development, severity of coronary artery disease, and the proportion of patients with congestive heart failure or bundle branch block. Patients who presented without cardiac arrest, however, more frequently had left ventricular aneurysms (58% vs 28%; p = 0.005). Sixty-seven patients underwent baseline drug-free electrophysiologic studies. Sustained ventricular tachycardia was induced in 79% of patients in the CA group and 85% of patients in the No CA group (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)


Defibrillation electrode configurations developed from cardiac mapping that combine biphasic shocks with sequential timing. Previous canine mapping studies of the transvenous defibrillation lead configuration of right ventricle (RV) to left R2 patch (P) revealed regions of low potential gradient in the left ventricular apex (A) and the right ventricular outflow tract (O). Thus 16 new lead configurations were tested in eight dogs, which incorporated electrodes in A and O to raise the gradient. When used in conjunction with two sequential biphasic shocks, the average defibrillation threshold energy from these configurations was 57% lower than that produced by a single biphasic shock delivered through RV-->P (phase 1 cathode-->anode, p < 0.001). Of the 16 configurations tested, the most effective was RV-->P followed by A-->O. When the shocking order of this configuration was reversed in another eight dogs, no difference in defibrillation efficacy was noted. In individual configurations of RV-->P and A-->O that used a single biphasic shock, defibrillation was not effective. Finally, when two sequential biphasic shocks were delivered to the same two electrodes in seven other dogs, the defibrillation efficacy was low. Thus configurations that use two sequential biphasic shocks can produce low defibrillation thresholds when the shocks are delivered to two different sets of electrodes. The high efficacy may be caused by one shock increasing the potential gradient in regions of low potential gradient that are produced by the other shock.


Outcome of endocardial resection in 33 patients with coronary artery disease: correlation with ventricular tachycardia morphology. The results in 33 patients with ventricular tachycardia (VT) treated by endocardial resection were reviewed, with special emphasis on the presence of single or multiple morphologies preoperatively and intraoperatively. Multiple VT morphologies were induced in 16 patients and a single VT morphology was induced in the remaining 17. Intraoperative programmed stimulation failed to induce VT in eight patients and visually-directed endocardial resection was performed. The remaining patients underwent map-guided resection. The surgical success rate did not correlate with any morphologic characteristics of the VT, such as bundle branch block pattern or axis. In addition, concordance of VT morphologies preoperatively and intraoperatively before resection did not correlate with the surgical success rate. However, patients in whom multiple morphologies of VT were induced intraoperatively had a significantly higher success rate (100%) compared with those patients in whom only a single morphology was induced intraoperatively (50%, p < 0.05). Long-term follow-up was maintained in 26 patients. Ventricular tachycardia recurred in two patients and VF recurred in two others who did not have inducible VT 1 week after endocardial resection. In conclusion, neither the preoperative morphologic characteristics of VT nor discordance between the morphologies of VT induced preoperatively and in the operating room influenced the outcome of endocardial resection. However, the surgical success rate is higher when multiple morphologies of VT are inducible in the operating room than when only one VT morphology is inducible.


Irregular ventricular tachycardia: a possible manifestation of longitudinal dissociation within the reentry pathway. Sustained monomorphic ventricular tachycardia is usually regular; that is, it is associated with constant R-R intervals. In several cases, however, the cycles of ventricular tachycardia are more or less variable. Fifty-four cases of sustained monomorphic ventricular tachycardia were evaluated in order to assess whether tachycardia was regular. Nine cases were defined as irregular (i.e., the R-R cycles varied by more than 40 msec throughout a 1-minute recording). In five cases tachycardia was "regularly irregular," since the R-R cycles could be divided into two separate groups: the group of long cycles and that of short cycles. In these cases the variability manifested according to a defined and constant pattern: bigeminal pattern (alternation of short and long cycles), trigeminal pattern (two short cycles followed by a long cycle), and so on. The regular variability of tachycardia cycle length suggests one of the following possibilities. (1) There are two alternative circuits (a short circuit and a long circuit) that share the same exit pathway. Whenever the reciprocating impulse runs through the short circuit, the R-R cycle is short; but if a block in the short circuit occurs, the impulse runs through the long circuit, resulting in a long R-R cycle. (2) There is a longitudinal dissociation within the reentry circuit; two separate pathways with different inherent conduction velocities are present. When the impulse runs through the fast pathway, the R-R cycle is short; whereas when a block in the fast pathway occurs, the impulse traverses the slow pathway, resulting in a long R-R cycle.


Reversibility of left ventricular dysfunction after successful catheter ablation of supraventricular reentrant tachycardia. Fourteen patients (mean age, 48 +/- 19 years) with left ventricular dysfunction in the absence of underlying organic heart disease underwent catheter ablation (nine with direct-current energy and five with radiofrequency energy) to treat drug-refractory, symptomatic supraventricular reentrant tachycardia (mean duration of tachycardia, 22 +/- 17 years). Clinical tachycardias were accessory pathway-mediated tachyarrhythmia (12 patients) and atrioventricular nodal reentrant tachycardia (two patients). Changes of ventricular function after successful ablation, as assessed by radionuclide ventriculography and echocardiography, showed a decrease in left ventricular end-systolic dimension (39 +/- 6 mm to 34 +/- 6 mm; 32 +/- 6 mm; p < 0.05) and in left ventricular end-diastolic dimension (55 +/- 5 mm to 52 +/- 3 mm; 51 +/- 3 mm; p < 0.05) in the early (2 to 3 months) and late (6 to 8 months) follow-up periods, increase of nuclear ejection fraction (38% +/- 8% to 46% +/- 7%; p < 0.05) and fractional shortening (28% +/- 7% to 36% +/- 8%; p < 0.05) in the late follow-up period. Increase of fractional shortening was mainly due to decrease in the end-systolic dimension. These findings suggest that prolonged attacks of uncontrolled supraventricular tachycardia may result in left ventricular dysfunction, which is reversible after successful catheter ablation of the arrhythmias.


Noninvasive assessment of systolic and diastolic left ventricular function in patients with chronic severe anemia: a combined M-mode, two-dimensional, and Doppler echocardiographic study. Thirty-one patients with chronic severe anemia of more than 3 months' duration (hemoglobin less than 7 gm/dl) and no underlying heart disease were studied by means of M-mode, two-dimensional, and Doppler echocardiography; an equal number of normal control subjects was also studied. There are conflicting reports regarding the influence of chronic severe anemia on systolic myocardial function, but diastolic function has not been systematically assessed. It is also uncertain whether anemia alone can cause heart failure in a structurally normal heart. We therefore performed a detailed study of echocardiographic indexes of systolic and diastolic left ventricular function in these patients. We found that patients with anemia have significantly faster heart rates and lower diastolic and mean blood pressures than normal subjects. They also have a significantly elevated cardiac output and stroke volume and larger left ventricles. Left ventricular contractility, assessed by the end-systolic stress-dimension relationship, was enhanced. There was no systematic evidence of diastolic dysfunction by Doppler assessment of mitral inflow. There was also no clinical evidence of congestive heart failure. We conclude that chronic severe anemia leads to a hyperdynamic state with systolic hyperfunction and no impairment of diastolic function. Anemia does not lead to congestive heart failure in the absence of underlying heart disease.


Prognostic significance of Doppler-derived left ventricular diastolic filling variables in dilated cardiomyopathy. To determine the prognostic significance of pulsed wave Doppler-derived left ventricular diastolic filling velocity profiles and the relationship between Doppler variables and clinical functional status, the follow-up outcomes of 62 consecutive patients with dilated cardiomyopathy and symptoms of left ventricular dysfunction were analyzed. All patients had echocardiographic left ventricular end-diastolic dimension > or = 6.0 cm, fractional shortening < 25%, increased E pointseptal separation, and diffuse hypokinesia or akinesia. During a mean follow-up period of 30.5 +/- 13.9 months, 27 patients experienced cardiac events: 23 died of either progressive pump failure or an episode of sudden death and four required cardiac transplantation because of refractory heart failure. Peak early filling velocity (78 +/- 23 cm/sec vs 65 +/- 25 cm/sec; p < 0.03) was higher and late atrial filing velocity (34 +/- 13 cm/sec vs 55 +/- 19 cm/sec; p < 0.001) was lower in patients with cardiac events than in cardiac event-free survivors. The ratio of early to late transmitral filling velocities was higher (2.6 +/- 1.2 vs 1.5 +/- 1.3; p < 0.001), and the deceleration time of early diastole was shorter (133 +/- 48 msec vs 175 +/- 71 msec; p < 0.001) in patients with cardiac events. The cardiac event rate was significantly higher in patients with an early to late filling velocity ratio greater than 2 (77% vs 19%; p < 0.001) or a deceleration time less than 150 msec (58% vs 23%; p < 0.05) than in those without. Stepwise multivariate regression analysis revealed that the pattern of transmitral early to late filling velocity ratio was the only significant independent Doppler echocardiographic predictor of outcome for these patients. Repeat Doppler echocardiographic examinations, which were performed in 31 survivors after intensive treatment (mean, 38.6 +/- 6.5 months), showed that early filling velocity was decreased (55 +/- 20 cm/sec vs 75 +/- 25 cm/sec; p < 0.02), late atrial filling velocity was increased (74 +/- 27 cm/sec vs 57 +/- 21 cm/sec; p < 0.01), early to late filling velocity ratio was reduced (0.8 +/- 0.3 vs 1.7 +/- 1.3; p < 0.001), and deceleration time was prolonged (227 +/- 60 msec vs 167 +/- 82 msec; p < 0.01) in 18 patients with clinical functional improvement, whereas these measurements were unaltered in the remaining 13 patients whose functional status was unchanged or had deteriorated.(ABSTRACT TRUNCATED AT 400 WORDS)


Mild dehydration induces echocardiographic signs of mitral valve prolapse in healthy females with prior normal cardiac findings. This study was designed to investigate the hypothesis that mitral valve prolapse (MVP) can be induced after diuresis in women without the abnormality who have characteristic body habitus. Fifteen tall, slim, healthy female volunteers with a normal cardiac findings, echocardiogram, and history were investigated after mild diuresis with furosemide and after placebo. All subjects lost weight after furosemide and placebo administration; but mean weight loss was significantly greater after furosemide administration than after placebo administration. Echocardiography showed MVP in none of the 15 patients before treatment, in seven after administration of placebo, and in seven after administration of furosemide. Coaptation point prolapsed superior to the anulus in seven subjects with echocardiographically determined MVP. Left ventricular end-diastolic dimensions decreased significantly after placebo or furosemide administration in subjects in whom MVP developed compared with the measurement in those in whom MVP did not develop. Murmurs characteristic of MVP disappeared in all four rehydrated subjects and echocardiographic changes resolved in two of the five rehydrated subjects. Thus echocardiographically determined MVP can be induced by mild dehydration in women with phenotypic body habitus of MVP; changes may resolve with rehydration. Results suggest an explanation for variable physical examination findings in persons with MVP.


Prospective study of blood culture during transesophageal echocardiography. To ascertain the incidence and significance of bacteremia associated with transesophageal echocardiography (TEE), 132 consecutive patients (aged 17 to 73 years) free of apparent infection who were undergoing 135 transesophageal echocardiographic procedures from October 1990 to August 1991, were prospectively studied. For each procedure, two sets of blood cultures were obtained for culture 30 to 60 minutes before TEE, immediately after, and 180 to 240 minutes after the procedure. For each blood culture, 10 ml of venous blood was evenly inoculated into aerobic and anaerobic culture bottles and inoculated for 7 days using a radiometric system. A throat swab was obtained immediately before each procedure. Three of 270 preprocedure blood cultures were positive for Bacillus cereus, Staphylococcus simulans, and Peptostreptococcus species, respectively. No blood culture was positive in the immediate postprocedure period. Two of 270 late blood samples grew Staphylococcus epidermidis in the same patient. Nevertheless, the microorganisms isolated from blood cultures were different from those isolated from the throat swab. No patients had fever or evidence of infective endocarditis after TEE during the follow-up period. It is concluded that the incidence of TEE-related bacteremia is extremely low, and a general recommendation for antibiotic prophylaxis during TEE is not warranted.


Transesophageal contrast echocardiography and color flow mapping: methods of choice for the detection of shunts at the atrial level? The detection of shunts at the atrial level is important, and a reliable means of diagnosis is required. Precordial contrast echocardiography is usually performed to detect such shunts. To investigate the advantages of transesophageal echocardiographic techniques, we studied 167 consecutive patients with both precordial and transesophageal echocardiography, using two-dimensional imaging with contrast techniques (with and without a Valsalva maneuver) and color flow mapping. A patent foramen ovale was diagnosed in 31 patients, an atrial septal defect in 11 (7 with bidirectional shunts), and a pulmonary arteriovenous fistula in 3 patients. All right-to-left shunts were detected with transesophageal contrast echocardiography. With these results used as the gold standard, the sensitivity of combined precordial techniques was 37% and that of transesophageal color flow mapping 46%. All left-to-right shunts were detected by transesophageal color flow mapping. With these results used as the gold standard, the sensitivities of both precordial color flow mapping and a transesophageal negative right atrial contrast study were 27%. We conclude that transesophageal contrast echocardiography is the echocardiographic method of choice for the detection of a right-to-left shunt at the atrial level, which cannot be excluded by negative results on precordial study or on transesophageal color flow map study. A left-to-right shunt at this level is best detected by transesophageal color flow mapping.


Late death after arterial switch operation for transposition of the great arteries. Fifty-nine patients survived for more than 1 month after an arterial switch operation (ASO). Diagnoses in these patients included transposition of the great arteries in 27, transposition of the great arteries with ventricular septal defect in 28, and double-outlet right ventricle in four. There were six late deaths (10%) during the follow-up period, and all of them occurred suddenly and unexpectedly. Four of the six late deaths were in patients who had undergone ASO in the neonatal period. Late deaths occurred from 40 days to 10 months after the operation. Autopsies were performed in all six patients. The cause of these late deaths was acute myocardial infarction. Five patients died of subendocardial infarction resulting from stenosis of the left main coronary artery. On pathologic examination, a fibrocellular intimal thickening was noted at the proximal region of the right and left coronary arteries, which resulted in 80% stenosis on average.