Fibrinolysis during pregnancy. The pre- and postpartal changes

Our previous research as well as data in literature (Yuasas, Ishizawa M.--1992) emphasised increased plasma fibrinolytic activity (PFA) in women during labor. Starting from these data we have tried to observe plasma fibrinolytic activity studied through euglobulin lysis time (ELT) in women during pregnancy and after delivery. We studied 25 healthy pregnant women aged between 18 and 30 years which were tested in the seventh month, during labour and at 48 hours after delivery. Blood samples were taken from the antecubital vein by venous puncture. The study showed an increased PFA (shortened ELT) only during labor; in the seventh month and at 48 hours after delivery ELT had almost the same values.     

Efficacy and pharmacokinetics of gallopamil in patients with coronary artery disease

We prospectively studied 10 patients with stable exertional ischaemia, selected from a larger group of patients referred for suspected coronary artery disease or to detect residual ischaemia after myocardial infarction, to evaluate pharmacokinetic changes during chronic treatment with gallopamil and its correlation with clinical efficacy in patients with coronary artery disease. Our study consisted of a 1-week run-in single-blind placebo treatment and a 4-week single-blind gallopamil treatment. At the end of the run-in period patients underwent two different exercise tests, the first 2 hours and the second 7 hours after placebo administration. During active treatment all patients underwent two different exercise tests, the first 2 hours and the second 7 hours after gallopamil (50 mg) administration on the 1st and 28th days of gallopamil therapy. On the same days in eight of the patients we evaluated gallopamil pharmacokinetic changes. Our data revealed a rapid increase of unchanged gallopamil and its metabolite (norgallopamil) in the plasma, and a peak concentration of these substances about 2 hour after oral administration on both the 1st and 28th day of observation. Moreover, our results demonstrated an increase between the first and 28th day of treatment in peak concentration of unchanged gallopamil in the plasma, and of AUC 0-infinity and AUC o-c values during chronic treatment with gallopamil. Our clinical data showed an improvement in exercise results during gallopamil therapy related to increased concentration of the drug.     

One-week low-dose triple therapy vs. two-week medium-dose double therapy for H.pylori infection

BACKGROUND/AIMS: Our study is to compare a short-term low-dose triple therapy with a long-term medium-dose double therapy for H.pylori eradication. MATERIALS AND METHODS: One hundred and ten consecutive patients, suffering from dyspeptic symptoms, with H.pylori infection, were randomly allocated to one of the following 2 groups with different therapeutic regimens: A) omeprazole 20 mg/day for 7 days, tinidazole 500 mg bid for 7 days, clarithromycin 250 mg bid for 7 days (55 pts, 20 with peptic ulcer); B) omeprazole 20 mg bid for 14 days, amoxycillin 1000 mg bid for 14 days (55 pts, 28 with peptic ulcer). The "H.pylori status" was evaluated by means of histology, culture and urease test, at entry and 8 weeks after treatment. RESULTS: Two group A and one group B pts didn't complete the treatment. The H.pylori eradication was obtained in 38 pts of group A (71.69%) (C.I.95%: 55.19176-80.86293), in 31 of group B (58.49%) (C.I.95%: 42.32777-69.7017); on Intention-to-Treat analysis, the rate of eradication gave similar results. Side effects occurred in 9 pts of group A (16.98%), in 8 of group B (14.81%). CONCLUSIONS: Short-term low-dose triple therapy with omeprazole/tinidazole/clarithromycin has a better cost/benefit ratio than long-term dual therapy with omeprazole/amoxycillin in the H.pylori eradication, but it causes more side-effects.     

Left ventricular function and coagulation activity in healed myocardial infarction

We investigated the plasma levels of molecular markers for the thrombotic and fibrinolytic status in patients with healed myocardial infarction to determine the relation between left ventricular (LV) function and coagulation activity. Our findings demonstrated that the coagulation activity was increased in patients with healed myocardial infarction along with LV dysfunction, suggesting that anticoagulant therapy is considered in patients with severe LV dysfunction to prevent systemic thromboembolism.     

Tyrosine hydroxylase gene expression in the locus coeruleus of depression-model rats and rats exposed to short-and long-term forced walking stress

Abnormal brain noradrenergic function is thought to cause depressive illnesses which are sometimes manifested or aggravated under stressful conditions. To investigate the effect of chronic stress on noradrenaline (NA) synthesis in the brain we used in situ hybridization to examine the expression of tyrosine hydroxylase (TH) mRNA in the locus coeruleus (LC) of "depression-model rats" that exhibit reduced activity following exposure to long-term (14 days) forced walking stress (FWS). We also examined TH mRNA expression in rats stressed for 30 minutes, 3 hours and 1, 2 (short-term), 6 or 12 (long-term) days. The expression of TH mRNA increased markedly following 1 to 12 days of FWS, but not in rats exposed to FWS for 30 minutes or 3 hours. The expression also increased significantly in the depression-model rats, but not in the "spontaneous recovery rats" whose activity was restored after long-term stress. Our results suggest that NA synthesis remains high in the FWS-induced depression-model rats because of the high levels of TH mRNA expression in the LC. Our results also suggest that FWS is initially a mild stress but gradually becomes a severe form of unadaptable stress as reflected by delayed but persistent increases in TH mRNA expression.     

Circulatory support with pneumatic paracorporeal ventricular assist device in infants and children

BACKGROUND: Mechanical circulatory support in intractable heart failure in children has been limited to centrifugal pumps and extracorporeal membrane oxygenation: Since 1990 small adult-size pulsatile air-driven ventricular assist devices "Berlin Heart" (VAD) and, since 1992 miniaturized pediatric VAD (12, 15, 25, 30 mL pumps), have been used in our institution. Since 1994 the blood-contacting surfaces of the device system have been heparin-coated. In this report the experiences with VAD support in 28 children are presented. METHODS: In 28 children-ages between 6 days and 16 years-the Berlin Heart VAD has been applied for periods of between 12 hours and 98 days (mean, 16.9 days) aiming at keeping the patient alive and allowing for recovery from shock sequelae until later transplantation or myocardial recovery. There were three groups. Group I: with primary intention of "bridge-to-transplantation" in various forms of cardiomyopathy (n = 13) or chronic stages of congenital heart disease (n = 5). Group II: "Rescue" in intractable heart failure early after corrective surgery for congenital heart disease (n = 4) or in early graft failure after a heart transplantation (n = 1). Group III: "Acute myocarditis" (n = 5) aiming at either myocardial recovery or transplantation. Twelve were brought to the operating room under cardiac massage and 25 had been on the respirator for more than 24 hours. RESULTS: Twelve patients died on the system from sequelae of profound shock-multiorgan failure, sepsis, loss of peripheral circulatory resistance-or from hemorrhagic complications (n = 4) or brain death (n = 1). Thirteen patients (groups I and III) were transplanted after support periods of between 3 and 98 days with 7 long-term survivors living now up to 7.5 years (mean, 4.4 years). Three patients (groups II and III) were weaned from the system with two long-term survivors (both in group III). There were no patients in group II who survived and the "rescue" indication has been discarded for VAD since 1992. Such patients are since treated by extracorporeal membrane oxygenation (ECMO) in our institution. Out of the 8 patients placed on VAD during 1996 and 1997, 7 were successfully supported until transplantation or weaning. Thirteen patients were extubated and mobilized on the system. Whereas with the earlier systems thrombi in the blood pumps were seen in 15 instances and 2 patients suffered from thromboembolic complications, no thrombotic events occurred with the heparin-coated systems. CONCLUSIONS: After accumulating clinical experience and several technical improvements since 1990 the use of the pediatric Berlin Heart VAD has matured into a reliable and safe system to keep patients with otherwise intractable heart failure alive until complete myocardial recovery is reached or transplantation becomes feasible. Whereas heart failure early after cardiac operation is now primarily treated by ECMO, acute myocarditis appears to be a promising precondition for complete cardiac recovery during VAD support.     

CONSORT: an attempt to improve the quality of publication of clinical trials

The sickling of erythrocytes increases viscosity and reduces the rate of both local circulation and arterio-venous transit time. This causes occlusion of capillaries by "microthrombin". The occlusion is implicated in the multiplicity of vaso-occlusive complications of both acute and chronic nature. Whether or not anticoagulant therapy is warranted in these states has remained debatable. There is no clear evidence that there is an inherent coagulation disorder. Earlier studies indicate that fibrinolysis is normal in steady state sickle cell disease but decreased during sickle cell crisis. We studied fibrinolytic activity or euglobulin clot lysis time (ECLT) in 47 subjects, twenty six of them with homozygous sickle cell (HbSS) disease and 21 healthy controls of whom eighteen had the HbAA and three had the HbAS genotypes. The sex distribution was sixteen males to ten females for the HbSS and 13 males to eight females for the controls. Age range was 17-35 years for the HbSS and 25-35 for the controls. Means for basic haematologic parameters including platelets were also performed. Mean clot lysis time (MCLT) was 3.75 hours for the HbSS and 1.91 hours for the controls (normal range 1 1/2-4 hours). The difference in ECLT between patients and controls was statistically significant (p < 0.001). Fifty three and a half per cent of the HbSS fell above the upper limit of normal MCLT. All the 21 controls fell within normal range. There were also statistically higher values (p < 0.001) in HbSS as compared to the controls with regard to MCV, WBC count, and platelet count.     

Prospective study of neonatal genital mycoplasma colonization and infection

Genital mycoplasmas have been implicated in different neonatal diseases as pneumonia, sepsis and meningitis. This prospective study was conducted to specify their role in these diseases. POPULATION AND METHODS--A pharyngeal or tracheal swab specimen for mycoplasmas culture was obtained from 100 infants admitted consecutively to the Neonatal Care Unit (NCU) during the first 24 hours of life. Mycoplasma culture of blood and cerebrospinal fluid was also performed. Pharyngeal and/or tracheal specimens were collected again on days 5, 15 and 28 if the child was still in the NCU. Mycoplasma hominis (Mh) and Ureaplasma urealyticum (Uu) were identified by culture in a modified Hayflick's medium. RESULTS--Three-hundred and ten pharyngeal or tracheal swabs were obtained (100 on day 0, 89 on day 5, 72 on day 15 and 49 on day 28). Twenty-one infants had one or more positive swabs in the first five days of life (20 on day 0 and one on day 5); those forming the "Myco+" group and the others forming the "Myco-" group. Uu was isolated alone from 20 infants, associated with Mh from one. Both groups were similar for gestational age, birth weight, maternal fever during labor, prolonged rupture of the fetal membranes or chorioamnionitis and for the incidence of acute respiratory distress. There was a statistically significant difference for the route of delivery (chi 2 < 0.02). One blood culture (from 92 performed) was positive for Uu and another positive for Uu and Mh. Both children were cured without any specific mycoplasmacidal therapy. Three children had probable Uu infection and were also cured without specific therapy. CONCLUSIONS--A pharyngeal colonization with genital mycoplasmas is common in the first days of life (21%) but our data do not allow us to conclude that they are accountable for newborn infections.     

Morphology and function of preserved microvascular arterial grafts: an experimental study in rats

The aim of this study is to examine the morphology and function and small-caliber, arterial grafts after preservation in the University of Wisconsin solution (UW). Rat carotid arteries were stored in UW (n = 10) or in phosphate-buffered saline (PBS) (n = 10) for 1, 3, 7, and 14 days and were examined with light microscopy (LM) and scanning electron microscopy (SEM). Rat aortic preparations were stored in UW or PBS for 1 hour, 24 hours, 72 hours, 7 days, and 14 days and assessed for functional responses (stimulated contraction and endothelium-dependent relaxation). Segments (5 mm) of rat carotid arteries were stored in UW or PBS for 3 days, 7 days, and 14 days and orthotopically implanted as autografts and allografts. No immunosuppressive or anticoagulant agents were used. After 28 days of implantation, the grafts were assessed for patency and excised for LM and SEM. In UW, the endothelial layer remained intact up to 9 days of storage. In PBS, the endothelial layer showed deterioration after 1 day and was completely lost after 3 days. Functional responses were demonstrated to exist for as long as 7 days storage in UW. In PBS, no responses could be evoked after 24 hours storage. Autografts preserved in UW for 3 days (n = 6), 7 days (n = 6), and 14 days (n = 6) showed patency rates of 83.3%, 66.6%, and 66.6%, respectively, whereas patency rates of allografts were 66.6%, 33.3%, and 33.3%, respectively. Autografts stored in PBS for 3 days (n = 6), 7 days (n = 6), and 14 days (n = 6) showed patency rates of 33.3%, 33.3%, and 50%, respectively, whereas patency rates of allografts were 16.7%, 0%, and 33.3%, respectively. The UW preserved autografts showed normal morphology. All other groups showed vessel wall degeneration which in the allograft groups, were accompanied by lymphocellular infiltration. In conclusion, the endothelial layer and vessel wall of arteries are adequately preserved in UW. Functional responses are retained up to 14 days storage in UW, but, are lost after 24 hours storage in PBS. Autograft implantation studies accordingly show good performance of arterial segments preserved in UW, whereas allografts are subject to degradation as a result of rejection.     

Guidelines or potentially dangerous recommendations? The AANS/CNS Committee on Assessment of Quality. American Association of Neurological Surgeons. Congress of Neurological Surgeons

This report uses a mathematical modeling system to define optimal orthopedic coverage for trauma centers. Data from 2,325 patients treated with emergency orthopedic operations within 24 hours of admission at 78 randomly sampled and at four totally sampled verified centers were used to create a profile of (1) admission by month, day, and hour; (2) operation times; and (3) operation duration. The reason for operation included (1) open fracture or crush (809 patients); (2) irreducible dislocations (164 patients); (3) fracture with vascular injury (seven patients); (4) dislocation with vascular injury (17 patients); (5) compartment syndrome (11 patients); (6) femoral neck fracture in young patients (36 patients); (7) combination of categories 1 to 6 (70 patients); (8) fracture with multiple injuries (171 patients); and (9) urgent not emergent (1,040 patients). The program defined the frequency that an injured patient needing an orthopedic consult would wait beyond 30 minutes because the orthopedic surgeon was doing a trauma related operation at a center with one or two orthopedic surgeons on call. The probability that a patient cannot be seen promptly by one orthopedic surgeon in a center doing 25, 50, 75, 100, 200, and 300 emergency procedures per year is 0.17, 0.74, 1.6, 3.1, 12.5, and 28 patients per year. When two are on call, 1.3 patients, yearly, will wait more than 30 minutes in a center doing 300 emergency procedures. Thus, mandatory orthopedic backup call for a trauma center performing fewer than 100 emergent trauma procedures within 24 hours is unwarranted.     

Traumatic aortic transections: eight-year experience with the "clamp-sew" technique

BACKGROUND: Because traumatic aortic transection is associated with high mortality rates, great debate exists about the appropriate operative technique for treatment of patients who have acute traumatic aortic transection. METHODS: To determine the safety and efficacy of the "clamp-sew" method, we retrospectively reviewed our 8-year experience treating 75 patients who had aortic injuries secondary to blunt trauma. Seventy-one of these patients were treated surgically. The clamp-sew method was used in all of these operations. RESULTS: Aortic cross-clamp time averaged 24 minutes (range, 14 to 36 minutes), with 4/71 having times in excess of 30 minutes. One patient (clamp time, 28 minutes) became paraplegic. Significant associated injuries were seen in 51/75 patients (48/71 patients with operation), including intrathoracic (35 patients), orthopedic (28 patients), intraabdominal (24 patients), and central nervous system (17 patients) damage. No patient died within 24 hours of operation. Overall 30-day mortality was 12% (9/75), with 7/9 having two or more aforementioned associated injuries. Of these 7, 5 had central nervous system injuries. Two of 9 died within 30 days without two or more associated injuries: 1 Jehovah's Witness of low hemoglobin, and 1 patient of sepsis. CONCLUSIONS: Although any of several maneuvers may be appropriate in managing traumatic aortic injuries, the simple "clamp-sew" technique is a safe and effective method for the treatment of traumatic aortic transections.     

Serial changes of plasma plasminogen activator inhibitor activity in acute myocardial infarction: difference between thrombolytic therapy and direct coronary angioplasty

The fibrinolytic system is impaired in patients with acute myocardial infarction (AMI). The primary regulatory element of fibrinolytic activity is plasminogen activator inhibitor (PAI). There are no reports, however, on the serial changes of PAI activity after thrombolysis or coronary angioplasty in patients with AMI undergoing emergency coronary angiography. This study was designed to examine the difference in the change of fibrinolytic activity between patients with AMI who underwent thrombolytic therapy with recombinant tissue-plasminogen activator (rTPA) and those who underwent direct percutaneous coronary angioplasty (PTCA). We measured the serial changes of PAI activity and tissue plasminogen activator (TPA) antigen after rTPA therapy or direct PTCA. Twenty-two patients received emergency coronary angiography and were treated with rTPA intravenously. Twenty patients underwent direct PTCA. Plasma PAI activity levels were increased on admission and further increased within 24 hours in patients treated with rTPA and in those treated with direct PTCA. In the thrombolysis group, there were two peaks in plasma PAI activity levels (IU/ml) at 4 hours (27.0 +/- 2.9) and at 16 hours (25.6 +/- 2.5) after the initiation of rTPA infusion. However, in the direct PTCA group, there was one peak of PAI activity (IU/ml) at 16 hours (23.9 +/- 2.7) after the initiation of direct PTCA. In conclusion, the PAI activity has two peaks in the thrombolysis group and one peak in the direct PTCA group.     

Fibrinolysis in the blood of animals exposed to the chronic per os use of a heparin-urea complex

When given per os a complex heparin-urea produces in the organism an intensive anticoagulant and fibrinolytic background which makes itself manifest in 1 hour time and continues to exist for as long as 16 hours after the last (10th) introduction. Upon abolishing the intake of the complex the study figures for the coagulation, anticoagulation and fibrinolytic activity return back to their physiological level. Introduction per os of the complex heparin-urea did not cause any changes in the tissues of the liver, heart, lungs, spleen and kidneys, while administration by the same route of an equivalent amount of urea caused mainly an increased non-fermentative fibrinolysis in the kidneys.     

Effects of oophorectomy and hormone replacement therapy on ophthalmic artery blood flow velocity waveforms

Our objective was to compare ophthalmic artery flow velocity waveforms in unilateral oophorectomized patients not on hormone replacement therapy with findings in bilateral oophorectomized patients on hormone replacement therapy. Ten patients who underwent hysterectomy and unilateral oophorectomy and 10 women treated by hysterectomy and bilateral oophorectomy were studied using color and pulsed Doppler ultrasonography 1 day before and on days 7 and 28 after surgery. Serum estradiol levels were measured serially. Bilateral oophorectomy patients were given hormone replacement therapy (conjugated estrogen, 0.625 mg/day, and medroxyprogesterone acetate, 2.5 mg/day) orally starting on day 8 after surgery. The pulsatility index values of the ophthalmic artery in unilateral oophorectomy patients were 1.93 +/- 0.41, 2.10 +/- 0.26, and 1.68 +/- 0.27 for 1 day before and on days 7 and 28 after surgery, respectively. The pulsatility index values of the ophthalmic artery in bilateral oophorectomy patients were 1.99 +/- 0.39, 2.17 +/- 0.47, and 1.75 +/- 0.32 for 1 day before and on days 7 and 28 after surgery, respectively. No significant differences were found between pulsatility index values in the unilateral and bilateral oophorectomy patients in each time period. The pulsatility index values on day 28 decreased significantly compared with the findings on day 7 in both groups (P < 0.05). The serum estradiol levels were significantly reduced from 1 day before to day 7 day after surgery and were significantly elevated by day 28 after surgery (P < 0.05) in both groups of patients. No significant differences were found between the serum estradiol levels in the unilateral and bilateral oophorectomy patients in each time period. Vascular tone in the ophthalmic artery seems to change according to serum estradiol levels, a finding that may help explain some of the beneficial effects of hormone replacement therapy for bilateral oophorectomized patients.     

Use of allografts in knee reconstruction: II. Surgical considerations

This paper aims to review current literature on the treatment of acute intraventricular hemorrhage in adults with intraventricular infusion of fibrinolytic agents. A literature search on the topics of "intraventricular hemorrhage" or "intracerebral hemorrhage" with "thrombolytic therapy", "fibrinolytic therapy", "urokinase", "streptokinase", "tissue plasminogen activator" or "tPA" covering the years 1966-1997 was carried out electronically. This was supplemented by searching the reference lists of the identified articles. Articles regarding exclusively intracerebral hemorrhage or hematoma, neonatal intraventricular hemorrhage, non-therapeutic issues, and laboratory research were excluded. The included articles are summarized in evidence and evaluation tables. Six articles evaluating the treatment of intraventricular hemorrhage in adults with intraventricular fibrinolytic agents were identified. One reports a small randomized clinical trial including 16 patients and appears to show a statistically insignificant preference for urokinase treatment. Five other reports present case series for which a total of 58 patients were exposed to either streptokinase, urokinase, or recombinant tissue plasminogen activator (rt-PA) and suggest good outcome. Two of them were with non-randomized retrospective or prospective controls, and three have no controls. Despite important limitations, all reports suggest that blood is more rapidly cleared from the ventricles and outcome is better when administering a fibrinolytic agent intraventricularly. While the experience presented in these papers suggests that intraventricular administration of fibrinolytic agents may be associated with fewer complications, more rapid clearing of blood from the ventricles, less late hydrocephalus, and better long-term outcome than is seen in patients treated with ventricular drainage alone, it is insufficient to recommend such treatment as a matter of policy. Substantial methodologic flaws render these findings suggestive at best. If the suggestive findings of these studies were confirmed in well-designed randomized clinical trials, an important impact on clinical practice could be expected.     

Doxorubicin cardiotoxicity in children: comparison of a consecutive divided daily dose administration schedule with single dose (rapid) infusion administration

Kyphoscoliosis surgery is frequently associated with major blood loss and coagulation disorders. A patient with juvenile rheumatoid arthritis, heart valve prosthesis and respiratory restrictive syndrome, was submitted to surgical correction of kyphoscoliosis. Current drug therapy included digitalis, oral anticoagulant and nonsteroidal anti-inflammatory drugs. After careful preoperative evaluation, oral anticoagulant and nonsteroidal anti-inflammatory drugs were discontinued (five and ten days before surgery, respectively), and intravenous heparin was introduced and maintained until two h before surgery. Bacterial endocarditis prophylaxis was obtained with ampicillin (50 mg.kg-1) and gentamicin (1.5 mg.kg-1). Anaesthetic management followed a general, balanced technique and the use of invasive monitoring devices. Clotting times were kept within the normal range--prothrombin time between 13 s and 14 s; partial thromboplastin time between 28 s and 30 s. Surgery was straightforward. The patient remained ventilated for 24 h and intravenous morphine (6 micrograms.kg-1.h-1) was used for nurse controlled analgesia. Afterwards, this was changed for patient controlled analgesia. Intravenous heparin was restarted 12 h after surgery and there were no complications postoperatively. Keeping the patient without anticoagulant therapy during this kind of surgery, was the less harmful option, taking into consideration that haemorrhage is inevitable and thromboembolism is a potential, though serious risk.     

Phase I evaluation of zidovudine administered to infants exposed at birth to the human immunodeficiency virus

This study evaluated the safety, tolerability, and pharmacokinetics of zidovudine administered intravenously and orally to infants born to women infected with the human immunodeficiency virus. Thirty-two symptom-free infants were enrolled before 3 months of age. The pharmacokinetics of zidovudine were evaluated in each infant after single intravenously and orally administered doses of zidovudine on consecutive days, and during long-term oral administration of the drug for 4 to 6 weeks. As new patients were enrolled, doses of zidovudine were progressively increased from 2 to 4 mg/kg. Therapy was continued for up to 12 months in 7 of the infants proved to be infected with human immunodeficiency virus. Zidovudine was generally well tolerated; 20 children (62.5%) had anemia (hemoglobin level < 10.0 gm/dl) during therapy and 9 (28.1%) had neutropenia (neutrophil count < or = 750 cells/mm3); these hematologic abnormalities usually resolved spontaneously. The total body clearance of zidovudine increased significantly with age, from an average of 10.9 ml/min per kilogram in infants < or = 14 days of age to 19.0 ml/min per kilogram in older infants (p < 0.0001). Concurrently, there was a significant decrease in serum half-life from 3.12 hours in infants < or = 14 days to 1.87 hours in older infants (p = 0.0002). Oral absorption was satisfactory and bioavailability decreased significantly with age, from 89% in infants < or = 14 days to 61% in those > 14 days of age (p = 0.0002). Plasma concentrations of zidovudine were calculated to be in excess of 1 mumol/L (0.267 micrograms/ml) for 4.12 +/- 1.86 hours and 2.25 +/- 0.78 hours after oral doses of 2 mg/kg in infants younger than 2 weeks and 3 mg/kg in older infants, respectively. We conclude that zidovudine administered at oral doses of 2 mg/kg every 6 hours to infants aged less than 2 weeks and 3 mg/kg every 6 hours to infants older than 2 weeks resulted in plasma concentrations that are considered virustatic against human immunodeficiency virus. Zidovudine was well tolerated by infants at these doses.     

Proliferating cell nuclear antigen (PCNA) expression in oral squamous cell carcinoma - an aid to conventional histological grading?

Decreased oxygen delivery and cellular hypoxia are major factors in the pathophysiology of shock. We studied the effects of 100% O2 at 0.1 and 0.3 MPa (1 and 3 atm abs) in severe hemorrhagic shock in awake, unrestrained rats. Shock was induced by withdrawing 50% of the total blood volume within 120 min. Blood pressure, heart rate, and the electroencephalogram (EEG) were recorded during the first 6 h of the protocol. The animals were observed for 7 days. The shock protocol resulted in 60 and 90% mortality after 1 day and at the end of 7 days, respectively. A single 90-min exposure to O2 at 0.1 and 0.3 MPa, which was started 30 min after bleeding, maintained mean arterial blood pressure at significantly higher values compared to untreated controls throughout the exposure period (P < 0.05). Oxygen therapy at both doses also improved the long-term survival rate and survival time significantly (P < 0.01). No clinical or EEG sign of CNS O2 toxicity was detected in O2-treated animals. Our results indicate that O2 given alone after severe bleeding exerts a beneficial effect on the long-term outcome of hemorrhagic shock in awake, unrestrained rats.     

Deep venous thrombosis complicating a congenital absence of the inferior vena cava

BACKGROUND AND PURPOSE: The use of left ventricular assist devices has become an established method in bridging patients with end-stage cardiac failure to heart transplantation. Since thromboembolism is one of the major complications, we undertook this study to evaluate the clinical significance of Doppler microembolic signals (MES) in patients with left ventricular assist devices. METHODS: Six patients with left ventricular assist devices were monitored for MES with transcranial Doppler ultrasonography during the first 30 postoperative days. Additionally, repeated (10 per day and patient) and prolonged (3 hours per patient) monitorings were performed to assess the adequacy of the 30-minute recordings. Three observers evaluated 30 randomly assigned monitorings in a blinded fashion to assess the interobserver variability. The relation between MES counts and clinical, radiological, hemostaseological, and pump flow parameters and the predictive value of MES counts regarding the occurrence of embolic events was evaluated. RESULTS: Ten ischemic cerebrovascular accidents and 2 peripheral thromboembolic events occurred during the observation period of 177 days (total incidence, 6.8%). MES were found in 143 of 170 monitorings (84.1%). Their counts were significantly higher on days with clinically manifest embolic events as compared with event-free days (18.5 [3-74] versus 4 [0-52], respectively, median and 95% CI; P < .001, Mann-Whitney). The predictive value of MES counts above 7 per 30 minutes was high (75%). Significant differences in the incidence and counts of MES as well as in the incidence of clinically manifest embolic events were noted among the six patients (all P < .01) without equal differences in anticoagulant treatment or pump flow. Interobserver agreement was high (p = .78 to .89, unpaired Student's t test). Considerable short- and long-term intrapatient variations of MES counts, without consistent pattern, were noted. CONCLUSIONS: Serial monitoring for MES is prognostically superior to single monitorings in patients with left ventricular assist devices. In the future, this new application mode may individually guide anticoagulation strategies and even influence the decision regarding early cardiac transplantation versus long-term use of the assist devices.     

Cholesterol or triglyceride loading of human monocyte-derived macrophages by incubation with modified lipoproteins does not induce tissue factor expression

Macrophages/foam cells localized in cholesterol- and triglyceride-rich regions of atherosclerotic plaques express high levels of tissue factor (TF), the essential cofactor and receptor of factor VIIa. It is not clear whether modified lipoproteins, for which several agonistic effects on macrophages have been described, are independent stimuli of TF expression in these cells. Therefore, we studied the effect of short-term (1 day) and long-term (4 to 7 days) incubation of human monocyte-derived macrophages cultured in suspension with modified and native LDLs or VLDLs on the expression of TF mRNA, antigen, and activity. We used native LDL or VLDL, moderately oxidized LDL or VLDL, severely oxidized LDL or VLDL, acetylated LDL, and beta-VLDL at a protein concentration of 100 microg/mL. Cholesterol loading occurred within 9 hours after the addition of acetylated LDL and continued during long-term incubation. Incubation of severely oxidized LDL for 7 days resulted in a slight increase in cholesterol content. Triglyceride loading was observed during short-term and long-term incubation with native and modified VLDLs. Neither cholesterol nor triglyceride loading resulted in expression of TF. Bacterial LPS still could induce TF expression in lipid-laden macrophages. Our results show that incubation with modified lipoproteins or lipid loading does not lead to TF expression in monocyte-derived macrophages cultured in suspension. This suggests that induction of TF expression in foam cells in the atherosclerotic lesion is triggered by additional or other components.