Evaluation of platelet function and tissue plasminogen activator activity in ischemic heart disease depending on concurrence with hyperlipoproteinemia and aspirin therapy

Platelet activation, impairment of fibrinolysis and dyslipidemia are important factors in the pathogenesis and progression of ischemic heart disease. Aspirin therapy will reduce platelet activation both by its negative effect on platelet aggregation (SPA) and by inhibition of granule release which liberates such mediators as platelet factor 4 (PF4) and plasminogen activator inhibitor 1 (PAI-1). The present study was performed in 57 patients with ischemic heart disease (IHD), divided into groups depending on coexistent hyperlipoproteinemia (HLP) and aspirin treatment. The control group included 21 healthy individuals, matched for age and sex. Parameters of hemostasis (SPA, PF4, PAI-1) and concentration of lipid fractions (TC, TG, LDL, HDL) were measured in plasma. Increased PF4 levels were found in all groups with IHD, irrespective of hyperlipoproteinemia or aspirin treatment. Enhanced SPA and higher PAI-1 were limited to group IHD-HLP without aspirin. Highest PAI-1 activities were observed after stimulation of platelets in vitro. In conclusion, patients with IHD and hyperlipoproteinemia presented most pronounced platelet activation and impairment of fibrinolysis. Aspirin had a beneficial effect on these changes. Lower activities of PAI-1, in patients treated with aspirin, can be ascribed to its reduced release from platelets. Aspirin did not satisfactorily reduce the level of PF4, although it strongly inhibited SPA.     

Long-term effects of ventilation tubes for persistent otitis media with effusion in children

OBJECTIVE: To analyze the clinical and scintigraphic features in four postoperative patients with lower limb edema. DESIGN: Four case reports are presented, and causes of increased lymphatic flow are discussed. MATERIAL AND METHODS: Filtered 99mTc-sulfur colloid (0.1 mL; 20 MBq) was administered by subcutaneous injection into the second web space of each foot. Sequential local (inguinal) and whole-body imaging was performed periodically up to 24 hours after the injections. The patients were three women who were 40, 51, and 86 years of age and an 81-year-old man. RESULTS: Each patient had unilateral lower extremity swelling and had recently undergone an ipsilateral lower limb operation. One female patient had previously undergone proximal femoral vein ligation, and another female patient had venous insufficiency demonstrated by Doppler ultrasonography. The male patient had a history of severe arterial insufficiency, and the remaining female patient had no venous or arterial abnormalities. On lymphoscintigraphy, all patients showed increased lymphatic flow in the edematous lower limb. Only the male patient also demonstrated abnormal dermal backflow pattern. CONCLUSION: Increased lymphatic flow most likely is a normal response to lower limb edema in the presence of normal peripheral lymphatic structures. In the four described cases, a recent lower limb surgical procedure may have resulted in disturbance of normal proximal lymphatic channels. The role of sympathetic innervation of the peripheral lymphatic system is a potential factor determining lymphatic response to trauma or surgical intervention. Increased flow on lymphoscintigraphy may not necessarily represent normal flow, especially if other scintigraphic features of abnormal lymphatic function-such as dermal backflow pattern-are present.     

Expression of CD2 on porcine B lymphocytes

BACKGROUND/AIMS: Deposition of paramagnetic substances in basal ganglia, resulting in increased signals in T1-weighted magnetic resonance images (bright basal ganglia), is frequently seen in liver cirrhosis. The present study describes the prevalence of bright basal ganglia and its clinical significance in patients with long-standing portal vein thrombosis in the absence of liver cirrhosis. METHODS: Six patients with angiographically proven complete portal vein thrombosis and cavernomatous transformation without signs of acute or chronic liver disease were studied by magnetic resonance imaging of the brain, neuropsychiatric evaluation, psychometric tests, electroencephalography, and determination of arterial ammonia levels and of serum manganese concentrations from peripheral venous blood. RESULTS: Five out of six patients demonstrated increased signal intensity in the basal ganglia. Overt portal-systemic encephalopathy was not noted prior to or at the time of evaluation. Normal EEG results were recorded in all patients. Only one of the six patients had pathological results in at least two out of four psychometric tests. This latter patient had had a large right-sided brain infarction. Arterial ammonia concentrations were normal in four of the six patients; one patient with increased ammonia levels had concomitant renal insufficiency with azotemia. The other four patients had no relevant concomitant diseases. Serum manganese levels were non-significantly increased compared with a control group (p=0.06), but they were significantly correlated to basal ganglia signal intensity (R=0.88; p=0.02). CONCLUSIONS: Our results demonstrate that bright basal ganglia primarily represent shunt-induced alterations. They are not directly associated with disturbed liver function nor with portal-systemic encephalopathy.     

Acute poisoning with amphetamines (MDEA) and heroin: antagonistic effects between the two drugs

BACKGROUND: While pelvic arterial insufficiency, either acute or chronic, results in stereotypic clinical findings which may readily be reversed by indirect techniques of revascularization, few reports document the indications for, techniques of, and results following direct pelvic revascularization by reconstruction of the hypogastric artery. METHODS: Retrospective review of 8 patients with symptomatic pelvic arterial insufficiency undergoing direct hypogastric artery reconstruction during the period from 1984 to 1995. RESULTS: Eight patients underwent unilateral hypogastric artery reconstruction by bypass graft (3 patients) or endarterectomy and patch angioplasty (5 patients). One patient had immediate symptomatic relief of his symptoms, but was lost to follow-up after 1 month. One patient manifested no symptomatic improvement despite a technically successful operation. The remaining 6 patients experienced significant symptomatic relief that has persisted during follow-up from 3 months to 11 years postoperatively. Among 4 men in whom erectile impotence comprised one of the indications for intervention, 3 reported sustained restoration of sexual function. CONCLUSION: In properly selected patients, direct pelvic revascularization by hypogastric artery reconstruction may predictably and durably relieve symptoms of pelvic arterial insufficiency.     

Effects of chronic renal insufficiency and metabolic acidosis on glutamine metabolism in man

1. Arterial concentration and arterial-venous differences of glutamine across the kidney, forearm, hepato-splanchnic bed and brain were measured in patients with chronic renal insufficiency and in patients with normally functioning kidneys before and during chronic ammonium chloride acidosis. 2. In chronic renal insufficiency and in chronic metabolic acidosis there is a rise in glutamine release from the muscles and a suppression of glutamine uptake by the hepato-splanchnic bed and the brain. 3. In chronic renal insufficiency arterial glutamine concentrations is significantly increased in comparison with subjects with normal renal function and either normal acid-base balance or chronic metabolic acidosis. 4. In patients with chronic renal insufficiency the kidney extracts negligible amounts of glutamine, which cannot account for the renal ammonia production measured in the same patients.     

Elevated levels of basic fibroblast growth factor in patients with limb ischemia

Basic fibroblast growth factor (bFGF), a prototypic member of a family of heparin-binding growth factors, is angiogenic both in vitro and in vivo. Increased levels and activity of bFGF have been documented in a variety of diseases, including tumors. We sought to determine whether bFGF might be similarly elevated in patients with clinical evidence of limb ischemia. Serum was obtained at the time of percutaneous revascularization from patients with symptomatic peripheral vascular disease (46 procedures were performed on 40 patients). An enzyme-linked immunoassay specific for bFGF was used (limit of detection, 1 pg/ml; range in normal subjects, 0 to 5 pg/ml). Among the 40 patients (28 men, 12 women, mean age 70 years) studied, elevated circulating bFGF (> or = 10 pg/ml) was detected in 36 samples (78%); levels ranged from 10 to 310 pg/ml (mean +/- SEM = 62 +/- 12). In 16 (89%) of 18 patients with both rest pain and nonhealing ischemic ulcers, serum bFGF levels were elevated up to 30 times normal values. In conclusion, circulating levels of bFGF are elevated in patients with vascular insufficiency and may reflect a physiologic response to limb ischemia.     

N-Acetylcysteine potentiates nitroglycerin-induced reversal of platelet aggregation

N-Acetylcysteine (N-AC) potentiates the systemic and coronary hemodynamic and antianginal effects of nitroglycerin (NGT) in humans; NTG/N-AC reduces the incidence of acute myocardial infarction in patients with unstable angina pectoris. Although previous studies have demonstrated that NTG exerts antiaggregatory effects on platelets, little information is available concerning the possible potentiation by N-AC of NTG antiplatelet effects. In the present study, we examined the in vitro effects of NTG and the combination of NTG with N-AC on reversal of ADP-induced aggregation in platelet-rich plasma (PRP) obtained from normal subjects and patients with stable angina pectoris. We also examined the potential effect of background aspirin therapy on this interaction. NTG, added to platelets 0.5 min after the beginning of aggregation, suppressed the incipient aggregation and provoked the appearance of a disaggregation phase, resulting in a concentration-dependent reversal of platelet aggregation. Platelet responsiveness to NTG was significantly less (p < 0.01) in both groups of patients (receiving and not receiving aspirin) as compared with normal subjects. N-AC (10(-5) M), which did not in itself affect aggregation, induced a threefold potentiation (p < 0.05) of the antiaggregating effect of NTG that was similar in degree for all tested groups of individuals. This potentiation of the antiplatelet effects of NTG by N-AC may contribute to the efficacy of combined NTG/N-AC therapy in patients with acute ischemic syndromes.     

Patent foramen ovale is an important predictor of adverse outcome in patients with major pulmonary embolism

BACKGROUND: Right-to-left shunt through a patent foramen ovale is frequently diagnosed by contrast echocardiography and can be particularly prominent in the presence of elevated pressures in the right side of the heart. Its prognostic significance in patients with pulmonary thromboembolism, however, is unknown. METHODS AND RESULTS: The present prospective study included 139 consecutive patients with major pulmonary embolism diagnosed on the basis of clinical, echocardiographic, and cardiac catheterization criteria. All patients underwent contrast echocardiography at presentation. The end points of the study were overall mortality and complicated clinical course during the hospital stay defined as death, cerebral or peripheral arterial thromboembolism, major bleeding, or need for endotracheal intubation or cardiopulmonary resuscitation. Patent foramen ovale was diagnosed in 48 patients (35%). These patients had a death rate of 33% as opposed to 14% in patients with a negative echo-contrast examination (P=.015). Logistic regression analysis demonstrated that the only independent predictors of mortality in the study population were a patent foramen ovale (odds ratio [OR], 11.4; P<.001) and arterial hypotension at presentation (OR, 26.3; P<.001). Patients with a patent foramen ovale also had a significantly higher incidence of ischemic stroke (13% versus 2.2%; P=.02) and peripheral arterial embolism (15 versus 0%; P<.001). Overall, the risk of a complicated in-hospital course was 5.2 times higher in this patient group (P<.001). CONCLUSIONS: In patients with major pulmonary embolism, echocardiographic detection of a patent foramen ovale signifies a particularly high risk of death and arterial thromboembolic complications.     

Asymptomatic embolization in subjects with atrial fibrillation not taking anticoagulants: a prospective study

BACKGROUND AND PURPOSE: Embolism is believed to be the major cause of stroke in patients with nonvalvular atrial fibrillation (NVAF). The detection of asymptomatic embolic signals (ES) in individuals with NVAF might allow identification of patients at high risk of stroke and monitoring of therapy in individual subjects. We determined the frequency of asymptomatic ES in patients with NVAF who were not taking warfarin. METHODS: Bilateral transcranial Doppler recordings were made for 1 hour from the middle cerebral arteries of 111 successive patients with NVAF taking aspirin alone or no antithrombotic or anticoagulant therapy. Adequate recordings could be made in 86 patients. In 79 subjects, recordings were performed on a second occasion to study temporal variability. Recordings for a single hour were also made in 30 age-matched control subjects. RESULTS: ES were detected in 13 (15.1%) of NVAF subjects but in no control subjects (P=0.02). ES were detected both in subjects with symptomatic NVAF (4 of 30 [13.1%], P=0.04 versus controls) and asymptomatic NVAF (9 of 56 [16.1%], P=0.02 versus controls). There was no correlation between the presence of ES and smoking status, diabetes, hypertension, aspirin use, aspirin dose, symptomatic status, left atrial size, left ventricular function, or the presence of left atrial thrombus detected on transthoracic echocardiography. Repeating the recording increased the number of patients with ES to 21 (26.6%). On considering the results of both recordings, again there was no association for either recording between the presence of ES and smoking status, diabetes, hypertension, aspirin use, aspirin dose, age, symptomatic status, left atrial size, or left ventricular function. On repeating the recording, in the symptomatic group only 2 patients (8%) changed status, in contrast to 15 (29%) in the asymptomatic group. CONCLUSIONS: ES can be detected in patients with NVAF at a low frequency. Particularly in asymptomatic patients, ES show marked temporal variability. We found no correlation between the presence of previously reported clinical and echocardiographic markers of increased stroke risk and the presence of ES. This association requires further investigation before the clinical utility of this technique in patients with NVAF is decided.     

Serum amylase determinations and amylase to creatinine clearance ratios in patients with chronic renal insufficiency

Patients with severe chronic renal failure may have significant hyperamylasemia in the absence of clinical symptoms or signs of acute pancreatitis. Amylase to creatinine clearance (CA/CC) ratios were usually elevated in patients with chronic renal failure and were not helpful in evaluating the possibility of acute pancreatitis. The mean amylase to creatinine clearance ratio for the controls with normal renal function was 1.24 +/- 0.13. In patients with chronic renal failure, it was 3.17 +/- 0.42 (P less than 0.001). Serum amylase isoenzyme patterns revealed no difference in salivary to pancreatic isoenzyme ratios between normals (1.04 +/- 0.12) and patients with severe renal insufficiency without evidence of pancreatic disease (1.07 +/- 0.13). The isoenzymes were helpful in excluding the diagnosis of pancreatic in 1 renal failure patient whose hyperamylasemia was primarily salivary in origin and in confirming the diagnosis in another who had only a pancreatic band.     

Cardiac valve calcification in haemodialysis patients: role of calcium-phosphate metabolism

BACKGROUND: Cardiac valve calcification (VC) has been detected with increased frequency in haemodialysis (HD) patients, making it necessary to determine the potential pathogenic factors in uraemic patients. METHODS: A total of 92 chronic HD patients (39 female, 53 male) and 92 age and gender-matched nondialysis control subjects were evaluated by echocardiography and a severity score for VC was determined. Calcium phosphate metabolism was evaluated at the beginning of haemodialysis. RESULTS: We found a greater prevalence of VC in dialysis patients than in normal patients (mitral annulus 44.5% vs 10%, P = 0.02; aortic annulus 52% vs 4.3%, P = 0.01). HD patients with mitral calcification were found to be older than patients without calcification, were on long-term renal replacement therapy, had longer duration of predialysis arterial hypertension, had greater values of the highest value of mean calcium phosphate product in 6 successive months (CaxP) and the highest absolute value of calcium-phosphate product (CaxPmax). We also found a positive correlation between calcification score, age, and CaxP. No correlation was found between actual VC and arterial hypertension or parathyroid hormone. Multiple stepwise regression analysis selected age and CaxP as the most predictive parameters for mitral calcification (r = 0.47). Mitral calcification was associated more frequently with rhythm and cardiac conduction defects, valvular insufficiency and with peripheral vascular calcification. Aortic calcification was correlated with age (r = 0.42) and longer duration of predialysis arterial hypertension. CONCLUSION: Our study confirmed an increased prevalence of VC in HD patients and selected age and calcium phosphate product as the most predictive parameters. These findings support careful monitoring of calcium metabolism beginning at the early stages of end-stage renal failure to reduce the risk of heart disease.     

Diversity of the blocking effects of antisperm antibodies on fertilization in human and mouse

The blocking effects of complement-dependent sperm immobilizing antibodies in the sera of infertile women and monoclonal antisperm antibodies against humans and mice on fertilization were investigated. The hemizona assay (HZA) and sperm penetration assay (SPA) were used to study the inhibitory effects of sera from 22 infertile patients positive for sperm immobilizing antibodies. Use of these tests allowed us to differentiate whether the antibody blocked sperm-zona pellucida tight binding and/or sperm penetration into the ooplasm. The zona pellucida penetration assay (ZPA) was also used to study the effects of four monoclonal antibodies (mAbs) on human sperm penetration into the zona pellucida. Seven mAbs against murine spermatozoa were tested for their inhibitory effects on in-vitro fertilization (IVF) and HZA in mice. Of 22 patient sera with sperm immobilizing antibodies, 21 (95.5%) inhibited HZA attachment and penetration, whereas this did not occur in any of 13 patient sera without these antibodies. However, 19 of 22 (86.4%) patient sera with sperm immobilizing antibodies and eight of 13 (61.5%) patient sera without these antibodies inhibited the SPA. Two (2C6, 1G12) of four mAbs against human spermatozoa showed strong inhibitory effects in all the assays (HZA, ZPA and SPA). One mAb (3B10) did not inhibit HZA but blocked ZPA and SPA. Another mAb (H6-3C4) seemed to have no inhibitory effects on fertilization. Two (Vx 5 and Vx 8) of seven mAbs against murine spermatozoa inhibited IVF in mice but did not block mouse HZA. These findings suggest that antisperm antibodies block fertilization at specific stages. Some of them may inhibit sperm capacitation and thus prevent all processes of fertilization that follow. Some other antibodies may not affect capacitation and sperm binding to zona pellucida but inhibit the acrosome reaction, followed by the blocking of sperm penetration through zona pellucida and ooplasm.     

Detailed deletion mapping at chromosome 9p21 in non-small cell lung cancer by microsatellite analysis and fluorescence in situ hybridization

We describe a case of pulmonary embolism and ischemic stroke due to paradoxical embolism in a healthy young woman taking oral contraceptives to treat an ovarian cyst. It was not possible to identify the site of the thromboembolus. Ultrasound techniques played an important role in identifying the peripheral arterial obstructions and in diagnosing acute pulmonary hypertension. Transesophageal echocardiography provided detailed information on both the morphology and the evolution of the atrial thrombus straddling the foramen ovale within the aneurysmal interatrial septum. The patient was given anticoagulant treatment, initially with heparin and subsequently with warfarin over a period of six months. Repeated ultrasound controls showed no thrombus, regression of the signs of pulmonary hypertension and, lastly unchanged systemic arterial obstruction.     

Platelet aggregation in acute coronary syndromes: use of a new aggregometer with laser light scattering to assess platelet aggregability

PURPOSE: To describe the computed tomographic (CT) appearance of hepatic infarcts resulting from arterial insufficiency in native livers. MATERIALS AND METHODS: The authors retrospectively reviewed the clinical and imaging findings in 10 patients (five men, five women; age range, 28-70 years) with 14 hepatic infarcts seen over 3 years. CT scans were analyzed for infarct appearance, vessel patency, and evolution of infarct pattern over time. RESULTS: Hepatic infarction resulted from hepatobiliary surgery (n = 6), radiologic intervention (n = 3), and celiac occlusion secondary to antiphospholipid syndrome (n = 1). All 14 infarcts were of low attenuation, peripheral, and wedge-shaped. Occluded arterial vessels were identified in eight patients. Follow-up CT revealed infarct diminution with parenchymal atrophy and scarring (n = 5), progressive liquefaction (n = 2), or both parenchymal atrophy and progressive liquefaction (n = 1). CONCLUSION: Sudden interruption of hepatic arterial flow may cause acute native liver infarction. Patients at risk include those with underlying vascular disease who undergo complicated surgical procedures and those undergoing peripheral arterial embolization.     

Differential ulcus cruris diagnosis

Most leg ulcers are of venous or arterial origin (85%). Advanced chronic venous insufficiency is the most common underlying condition (65%), followed by advanced peripheral arterial occlusive disease (10%), and combined chronic venous insufficiency and peripheral arterial occlusive disease (10%). Chronic ulcers in diabetic feet (5%) are of great socio-economic importance, as well. They are a consequence of diabetic polyneuropathy which in part of the patients may be combined with peripheral arterial occlusive disease, usually of the calf arteries. However, a leg ulcer can also be caused by a large array of other underlying conditions, such as ulcerating skin tumours, trauma followed by disturbed wound healing, infectious ulcerations, ulcerations in angiodysplasias, vasculitic ulcerations, pyoderma gangrenosum, cholesterol-embolism, idiopathic livedo reticularis with ulceration, primary and secondary antiphospholipid-antibody-syndrome, coumarin-necrosis, calciphylaxis in chronic renal insufficiency, necrobiosis lipoidica, different forms of panniculitis, hematologic disorders, autoimmun diseases and autoimmun-bullous dermatoses. The following article discusses the differential diagnosis, examination and treatment of leg ulcers in these less common underlying conditions.     

Prevalence of aspirin use among patients calling 9-1-1 for chest pain

OBJECTIVE: Early aspirin administration during an acute myocardial infarction (AMI) decreases morbidity and mortality. This investigation examined the extent to which patients with a complaint of chest pain, the symptom most identified with AMI by the general population, self-administer aspirin before the arrival of emergency medical services (EMS) personnel. METHODS: In this prospective, cross-sectional prevalence study, data were derived through the analysis of EMS incident reports for patients with a complaint of chest pain from June 1, 1997, to August 31, 1997. RESULTS: The study included 694 subjects. One hundred two (15%) took aspirin for their chest pain before the arrival of EMS personnel. Of the 322 subjects who reported taking aspirin on a regular basis, 82 (26%) took additional aspirin for their acute chest pain. Only 20 (5%) of the 370 patients who were not using regular aspirin therapy self-administered aspirin acutely (p<0.001). In addition, patients with lower intensity of chest pain (p = 0.03) were more likely to take aspirin for their chest pain. CONCLUSION: Only a relatively small fraction of individuals calling 9-1-1 with acute chest pain take aspirin prior to the arrival of EMS personnel. These individuals are more likely to self-administer aspirin if they are already taking it on a regular basis. It is also possible that they are less likely to take aspirin if their chest pain is more severe.     

Aspirin-induced asthma and HLA-DRB1 and HLA-DPB1 genotypes

BACKGROUND: Aspirin-induced asthma (AIA) affects one in 10 individuals with adult-onset asthma. It is not known if aspirin sensitivity is due to immune mechanisms or to interference with biochemical pathways. OBJECTIVE: The study aimed to test for possible involvement of the genes of the Major Histocompatibility Complex (MHC) in AIA. METHODS: HLA-DPB1 and HLA-DRB1 genotyping was carried out by DNA methods in 59 patients with positive challenge tests for AIA and in 48 normal and 57 asthmatic controls. RESULTS: The DPB1*0301 frequency was increased in AIA patients when compared with normal controls (19.5% vs 5.2%, Odds Ratio = 4.4, 95% Confidence Interval (CI) 1.6-12.1, P = 0.002), and compared with asthmatic controls (4.4%, OR = 5.3, 95% CI = 1.9-14.4, P = 0.0001). The frequency of DPB1*0401 in AIA subjects was decreased when compared with normal controls (28.8% vs 49.0%, OR = 0.42, 95% CI = 0.24-0.74, P = 0.003) and asthmatic controls (45.6%, OR = 0.48, 95% CI = 0.28-0.83, P = 0.008). The results remained significant when corrected for multiple comparisons. There were no significant HLA-DRB1 associations with AIA. CONCLUSION: The presence of an HLA association suggests that immune recognition of an unknown antigen may be part of the aetiology of AIA.     

Does daily aspirin diminish severity of first-ever stroke?

BACKGROUND: There are still uncertainties about aspirin efficacy in first-ever ischemic stroke prevention. Also it is unknown whether the severity of first ischemic stroke can be modified by aspirin pretreatment. OBJECTIVE: To analyze a series of patients who had their first ischemic stroke while taking aspirin to evaluate the ability of aspirin prophylaxis to diminish the severity of first-ever ischemic stroke. DESIGN: Case-control study. SETTING: Tertiary medical center to which patients were referred. PATIENTS: All consecutive patients admitted to the Tel Aviv Medical Center, Tel Aviv, Israel, from May 1988 through May 1994 because of first-ever ischemic stroke were divided into 2 groups according to aspirin use before stroke: aspirin-treated and non-aspirin-treated groups. MAIN OUTCOME MEASURES: Stroke severity was defined according to activities of daily living within 24 hours after admission: (1) mild stroke, with independence in activities of daily living; (2) moderate stroke, with partial dependency; and (3) severe stroke, with complete dependency. Using chi 2 test, stroke severity was compared between patients taking aspirin before their stroke and non-aspirin-treated patients. RESULTS: Among 2113 consecutive patients with first-ever ischemic stroke, 125 patients had already been taking 100 to 500 mg of aspirin daily. Aspirin-treated and non-aspirin-treated patients did not differ in stroke severity. Mortality was lower in aspirin-treated patients (7.9%) than in non-aspirin-treated patients (12%), but this difference was not statistically significant (P = 17). CONCLUSIONS: We conclude that aspirin as primary prevention treatment has no significant protective effect on severity of first-ever ischemic stroke. The diminution of mortality after first ischemic stroke in patients who had used aspirin should be investigated further.     

So, what makes you want to be a nurse?

Plasmapheresis used in 61 patients with stage II hypertension brought a stable fall in arterial pressure and clinical response. Hypotensive drugs were reduced in doses or even discontinued. In subjects with hyperkinetic circulation arterial pressure went down due to decreased cardiac output. In hypokinetic hemodynamics hypotensive effect occurred because total peripheral resistance diminished. Lowering of arterial pressure was associated with positive changes in cerebral circulation. Plasmapheresis proved effective in all hypertensive subjects: in both hypo- and hyperkinetic circulation.     

Pharmacokinetic-pharmacodynamic modelling of the anti-lipolytic and anti-ketotic effects of the adenosine A1-receptor agonist N6-(p-sulphophenyl)adenosine in rats

1. The purpose of this study was to develop and validate an integrated pharmacokinetic-pharmacodynamic model for the anti-lipolytic effects of the adenosine A1-receptor agonist N6-(p-sulphophenyl)adenosine (SPA). Tissue selectivity of SPA was investigated by quantification of haemodynamic and anti-lipolytic effects in individual animals. 2. After intravenous infusion of SPA to conscious normotensive Wistar rats, arterial blood samples were drawn for determination of blood SPA concentrations, plasma non-esterified fatty acid (NEFA) and beta-hydroxybutyrate levels. Blood pressure and heart rate were monitored continuously. 3. The relationship between the SPA concentrations and the NEFA lowering effect was described by the indirect suppression model. Administration of SPA at different rates and doses (60 microg kg[-1] in 5 min and 15 min, and 120 microg kg[-1] in 60 min) led to uniform pharmacodynamic parameter estimates. The averaged parameters (mean+/-s.e., n=19) were Emax: -80+/-2% (% change from baseline), EC50: 22+/-2 ng ml(-1), and Hill factor: 2.2+/-0.2. 4. In another group, given 400 microg kg(-1) SPA in 15 min, pharmacodynamic parameters for both heart rate and anti-lipolytic effect were derived within the same animal. The reduction in heart rate was directly related to blood concentration on the basis of the sigmoidal Emax model. SPA inhibited lipolysis at concentrations lower than those required for an effect on heart rate. The EC50 values (mean+/-s.e., n=6) were 131+/-31 ng ml(-1) and 20+/-3 ng ml(-1) for heart rate and NEFA lowering effect, respectively. 5. In conclusion, the relationship between blood SPA concentrations and anti-lipolytic effect was adequately described by the indirect suppression model. For SPA a 6 fold difference in potency was observed between the effects on heart rate and NEFAs, indicating some degree of tissue selectivity in vivo.