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One hundred two patients with evolving myocardial infarction of 6 hours' duration were given aspirin and intravenous heparin and randomly allocated to intravenous front-loaded, weight-adjusted rTPA administration over a 90-minute period (52 patients) or to two 15 mg doses of recombinant staphylokinase, 30 minutes apart (50 patients). Thrombolysis in Myocardial infarction (TIMI) perfusion grade 3 at 90 minutes was achieved in 68% (95% confidence interval, 55% to 81%) of patients treated with staphylokinase versus 57% (95% confidence interval, 43% to 72%) of patients treated with rTPA (p = not significant). Double-bolus staphylokinase was significantly more fibrin-specific than accelerated rTPA with residual fibrinogen at 90 minutes of 105% +/- 4.1% and 68% +/- 7.5%, respectively (p < 0.0001). Thirteen patients in each study group underwent angioplasty of the culprit coronary artery within the first 24 hours because of suboptimal recanalization (TIMI < 3). In the patients without prior coronary intervention, TIMI 3 at 24 hours was 100% after staphylokinase administration (n = 35) versus 79% after rTPA (n = 34) (p = 0.005). The distribution of inhospital events did not significantly differ between both groups. One patient receiving rTPA died in the hospital from ischemic stroke. Staphylokinase administration did not induce allergic reactions, but significant staphylokinase-neutralizing activity (> 5 micrograms/ml) and specific anti-staphylokinase IgG developed in 73% of patients after 2 weeks. Thus two 15 mg doses of staphylokinase induce early, complete, and sustained coronary artery patency at least as frequently as accelerated rTPA without associated fibrinogen degradation but with subsequent induction of circulating neutralizing antibodies.

Photolithographic micromachining of silicon is a candidate technology for the construction of high-throughput DNA analysis devices. However, the development of complex silicon microfabricated systems has been hindered in part by the lack of a simple, versatile pumping method for integrating individual components. Here we describe a surface-tension-based pump able to move discrete nanoliter drops through enclosed channels using only local heating. This thermocapillary pump can accurately mix, measure, and divide drops by simple electronic control. In addition, we have constructed thermal-cycling chambers, gel electrophoresis channels, and radiolabeled DNA detectors that are compatible with the fabrication of thermocapillary pump channels. Since all of the components are made by conventional photolithographic techniques, they can be assembled into more complex integrated systems. The combination of pump and components into self-contained miniaturized devices may provide significant improvements in DNA analysis speed, portability, and cost. The potential of microfabricated systems lies in the low unit cost of silicon-based construction and in the efficient sample handling afforded by component integration.

Suboptimal lipolysis of very low density lipoproteins (VLDL) due to reduced substrate affinity for lipoprotein lipase (LPL) may contribute to the accumulation of apolipoprotein (apo) B in familial combined hyperlipidemia (FCH) or the characteristic increase in triglyceride-rich lipoproteins in familial hypertriglyceridemia (FHTG). To investigate this hypothesis in detail, the VLDL composition and substrate affinity for lipoprotein lipase was determined in 22 normolipidemic controls, 16 FCH probands, and 12 FHTG subjects. VLDL from FCH subjects were enriched in cholesterol and phospholipid. VLDL from FHTG subjects were enriched in triglycerides, cholesterol and phospholipid. Potential apolipoprotein regulators of LPL activity including apo C-II, apo C-III and apo E were not significantly different between FCH and controls when expressed per VLDL apo B. High apo C-III concentrations were present in FHTG-VLDL, and the apo C-III/E-ratio was significantly higher than in FCH- and control-VLDL. An increase of C-III-0, the desialylated isoform, was observed in FHTG-VLDL. The kinetic indicators for in vitro triglyceride hydrolysis by LPL, KM and VMAX, were not significantly different between the groups. KM values measured in vitro were remarkably and consistently high (1.54 mmol VLDL-TG/I), predicting saturation of LPL when VLDL-TG levels exceed 5.5 mmol/l (2 times KM + 2S.D.). In conclusion, VLDL from individuals with FCH or FHTG are normal substrate for lipoprotein lipase in spite of significant differences in lipid and apolipoprotein composition. The high apo C-III content of FHTG-VLDL supports a role in the expression of hypertriglyceridemia.

Non-insulin-dependent diabetes mellitus is frequently associated with premature atherosclerosis. Abnormalities in lipid and lipoprotein metabolism contribute to the increased risk of coronary heart disease. One of the most common lipid abnormalities in non-insulin-dependent diabetes mellitus is hypertriglyceridaemia. In the present paper, the authors review the metabolism of triglyceride-rich lipoproteins, with special emphasis on the post-prandial state. Several studies have demonstrated that levels of atherogenic post-prandial lipoproteins are increased in patients with non-insulin-dependent diabetes mellitus. An increased supply of glucose and free fatty acids contributes to overproduction of very low-density lipoproteins, increasing the burden of triglyceride-rich lipoproteins on the common lipolytic pathway at the level of lipoprotein lipase. Low lipoprotein lipase activity and increased amounts of lipolysis-inhibiting free fatty acids further impair lipolysis of post-prandial lipoproteins. The clearance of atherogenic remnants is also delayed in non-insulin-dependent diabetes mellitus. There is evidence that a relative hepatic removal defect exists, secondary to impaired remnant-receptor interaction and increased competition with very low density lipoprotein remnants. Correction of the increased post-prandial lipaemia in non-insulin-dependent diabetes mellitus is advisable, as it may contribute to attenuation of the risk on premature atherosclerosis. When dietary measures and hypoglycaemic agents have failed to achieve acceptable lipid levels, lipid-lowering drugs should be advised. Fibric acids and hydroxymethyl-glutaryl coenzyme A (HMG CoA) reductase inhibitors are the drugs of choice.

Helicobacter pylori is one of the main causes of type B gastritis and is frequently found in the gastric antrum or in areas of gastric metaplasia in duodenal ulcer patients. The aim of this study was to evaluate Helicobacter pylori and gastric metaplasia prevalence in duodenal ulcer patients within their first diagnosed episode compared to those with chronic ulcer disease. Eighty three patients were prospectively studied in a 2-year period, they were divided into 3 groups: Group I, control, included 29 patients; Group II, 17 patients, included patients with first diagnosed duodenal ulcer episode; and Group III, 37 patients, with chronic ulcer disease. Helicobacter pylori prevalence in duodenum was significatively lower in Group II versus Group III and controls (67.5%, 0% and 3.2% respectively) (p < 0.001). In the antrum Hp prevalence was also lower in Group II compared to Group III and I (41%, 78.3% and 24.1%) with a significative difference (p < 0.001). Gastric metaplasia was significantly higher in Group III versus Group II and controls. These results suggest that Helicobacter pylori plays an important but not exclusive role in the pathogenesis of these disease together with other factors.

Background: Recombinant staphylokinase (STAR) was shown recently to offer promise for coronary arterial thrombolysis in patients with evolving myocardial infarction. The present multicenter randomized open trial was designed to assess the thrombolytic efficacy, safety, and fibrin specificity of STAR relative to accelerated alteplase (recombinant tissue-type plasminogen activator [RTPA])., Methods and Results: One hundred patients with evolving myocardial infarction of < 6 hours' duration and with ST-segment elevation were allocated to accelerated and weight-adjusted RTPA over 90 minutes (52 patients) or to STAR (the first 25 patients to 10 mg and the next 23 patients to 20 mg given intravenously over 30 minutes). All patients received aspirin and intravenous heparin. The main end points were coronary artery patency and plasma fibrinogen levels at 90 minutes. Thrombolysis in Myocardial Infarction (TIMI) perfusion grade 3 at 90 minutes was achieved in 62% of STAR patients versus 58% of RTPA patients (risk ratio, 1.1; 95% CI, 0.76 to 1.5). With 10 mg STAR, TIMI grade 3 patency was 50% (risk ratio, 0.86; 95% CI, 0.54 to 1.4 versus RTPA); with 20 mg STAR, it was 74% (risk ratio, 1.3; 95% CI, 0.90 to 1.8 versus RTPA). Residual fibrinogen levels at 90 minutes were 118 +/- 47% (mean +/- SD) of baseline with STAR and 68 +/- 42% with RTPA (P < .0005). STAR therapy was not associated with an excess mortality or electric, hemorrhagic, mechanical, or allergic complications. However, patients developed antibody-mediated STAR-neutralizing activity from the second week after STAR treatment. As an addendum to the randomized study, 5 patients were given 40 mg STAR over 30 minutes, resulting in TIMI perfusion grade 3 at 90 minutes in 4 patients without fibrinogen breakdown (residual levels at 90 minutes of 105 +/- 8% of baseline)., Conclusions: STAR appears to be at least as effective for early coronary recanalization as and significantly more fibrin-specific than accelerated RTPA in patients with evolving myocardial infarction.

An elderly women presenting with transient ischemic events underwent transesophageal echocardiography, which detected an aneurysm of the interatrial septum. A tumor protruding from the right atrial aspect of the aneurysm also was found incidentally. Not only was magnetic resonance (MRI) imaging helpful in better characterizing the aneurysm, but also the use of gadolinium diethylaminetriamine pentaacetic acid permitted differentiation between the tumor and adherent thrombus. To the best of our knowledge, this represents the first report of a tumor arising from an atrial septal aneurysm.

Infective endocarditis causes substantial morbidity and mortality despite adequate antimicrobial, medical and surgical treatment. The rationale for antibiotic prophylaxis against endocarditis is derived from the etiology and pathogenesis of the disease. Endocarditis usually follows bacteremia with certain endocarditis-prone bacteria in a patient with a predisposing heart condition. Protection by antibiotic prophylaxis is estimated to reach only 50% for a lot of reasons (transient bacteremia without dental or surgical intervention, predisposing heart disease not diagnosed previously, etc). Most authorities in the field of infective endocarditis strongly advocate the use of antibiotic prophylaxis for patients at risk. Clear guidelines are published by various highly qualified scientific committees. Recent schemes allow orally administered antibiotic prophylaxis because of a better doctor and patient compliance.

Quantitation of coronary luminal diameter with a 20 MHz mechanically rotating intravascular ultrasound (IVUS) catheter was compared with orthogonal-view cineangiography by use of a semiautomated edge-detection algorithm in 48 patients undergoing coronary angioplasty. Quantitative comparison of 196 matched segments was attempted, but in only 174 (88.8%) was a direct comparison of the two techniques possible. In angiographically normal coronary arteries (46 segments) the correlation between the values obtained by quantitative coronary angiography (QCA) and those achieved by IVUS was excellent (r = 0.92, p < 0.0001). For mild stenoses (80 segments) the correlation coefficient was only fair (r = 0.467, p < 0.001). After percutaneous transluminal coronary angioplasty the correlation coefficient between IVUS and QCA data (48 segments) was very weak (r = 0.282, p < 0.05). In conclusion, coronary IVUS is feasible and safe and even for a limited range of coronary arterial narrowing, significant correlations between IVUS and QCA measurements of minimal lumen diameter were found. They were excellent in normal coronary arteries, moderate in mildly diseased arteries, and weak after balloon angioplasty.

Although selective contrast coronary arteriography has been the gold standard approach for coronary imaging since more than 30 years, new coronary imaging techniques are currently under development. Intravascular ultrasound (IVUS) is perhaps the most promising of these additional techniques. IVUS makes use of miniaturised crystals incorporated at catheter tips and provides real time, cross-sectional and longitudinal, high resolution images of the arterial wall with three-dimensional reconstruction capabilities (Pandian, 1989; Coy et al., 1991; Liebsen & Klein, 1992). Different devices have been constructed. Actually two types are being used: mechanical (hand-rotated or motor-driven) systems and phased array systems using high-frequency (20-30 MHz) transducers (Bom et al., 1989). Coronary ultrasound imaging performed during catheterization is feasible and safe as demonstrated in several studies examining normal and pathologic coronary arteries (De Scheerder et al., in press).

Unlabelled: The value of intracoronary ultrasound for quantitative assessment of minimal coronary arterial diameter and for on-line evaluation of balloon angioplasty result was studied in 42 patients undergoing single vessel coronary angioplasty. Measurement of minimal luminal diameter of 75 matched coronary arterial segments showed a significant correlation between both the ultrasound and angiographic method (r: 0.759; p < 0.001). Furthermore using intravascular ultrasound it was possible to classify the obtained coronary balloon angioplasty results. A preliminary correlation between ultrasound classification and the in-hospital acute rethrombosis as well as late restenosis was attempted in individual patients., Conclusions: 1) Clinical use of coronary ultrasound is feasible and safe in selected cases. 2) A significant correlation between intracoronary ultrasound and quantitative coronary angiography is demonstrated. 3) Using intracoronary ultrasound seems promising for evaluation of the postangioplasty result, and may finally lead to improved selection of the interventional strategy.

In 9 out of 14 patients with chronic eosinophilic pneumonia (CEP), followed-up in our department, circulating immune complexes (CIC) and other immunologic indices were investigated. The diagnosis of CEP was based on the typical clinical and radiographic findings and on the demonstration of eosinophilia in serum, bronchoalveolar lavage (BAL), fiberoptic transbronchial biopsies and surgical lung biopsies. CIC measured by solid-phase monoclonal RF binding were always strongly positive during a flare-up of CEP, and CIC measured by solid-phase C1q binding were also positive in most cases. Remissions of CEP were accompanied by lowering or disappearance of CIC. CIC were significantly correlated with eosinophilia (p less than 0.001 for RF and p less than 0.02 for C1q). Other immunologic indices were normal except for increased IgE in two thirds of the patients, and a slightly positive rheumafactor without rheumatic disease in half of the patients. The CIC are thus related to disease activity, and can be used as one of the markers of it, in addition to the classical markers such as eosinophilia and chest X-ray. However, this does not imply that the CIC have a pathogenetic role in CEP; these CIC can, indeed, be an epiphenomenon only.

13 consecutive adult gastroenterological patients with non-malignant disease who were candidates for total parenteral nutrition (TPN), and who had mild protein-energy malnutrition (82 +/- 3% of ideal body weight, serum albumin 32 +/- 2 g/l, mean +/- SEM) were found to have, prior to TPN, a Selenium level 50% less than controls (p < 0.001) as assayed by Se and glutathione peroxidase (GSHPx) in plasma and erythrocytes. Compared with other trace metals and minerals, eg, Mn, Zn and Cu, depletion of Selenium was the most marked in this population. Patients were randomised to be supplemented with either 100 or 200 microg/d of sodium-selenite, equal to 32 microg (0.4 micromol) or 64 microg (0.8 micromol) of selenium, in two cross-over periods of TPN, each of two weeks. In this short term study, significant increases in the four measurements of Se status (p < 0.05) were seen in all patients, but there was no difference between those receiving the high or low dose of the element. GSHPx in plasma was normalised within 1 month whereas the increase seen in the erythrocyte pool was consistent with a 4-month half-life. Pooled Se values for patients and controls showed logarithmic correlations between Se and GSHPx in erythrocytes (p < 0.001) and plasma (p < 0.01). Changes in GSHPx provided further evidence of Se depletion in our patients. This study suggests that malnourished gastroenterological patients receiving TPN require Se supplements and that 100 microg (0.4 micromol)/d of sodium-selenite is adequate for most patients since there was no additional benefit from the higher dose of 200 microg (0.8 micromol).

Catheter-related sepsis is one of the most frequent and troublesome complications of parenteral nutrition. In a 2-year survey of 19 home parenteral nutrition patients, with a total of 25.2 years of cyclic nocturnal parenteral nutrition, the annual incidence of catheter-related sepsis was 1.27, of which 84% were due to bacterial catheter infection without any cutaneous focus. These 27 episodes were treated by a daily, 2 ml injection of antibiotic-saline solution, mainly amikacin, locked for 12 h per day within the infected catheter for 15 (7-20) days. On admission the parenteral nutrition was halted for 2 days and the catheter hub was changed. In 7 cases, an average of 3 days (2-5) of systemic antibiotic therapy was given in addition to the 2-week antibiotic-lock. Control of catheter-sepsis was achieved in 93% of the 27 episodes and parenteral nutrition was resumed using the same catheter with only one episode of recurrent sepsis. The present data confirm our preliminary report of the efficacy of the antibiotic-lock technique for the control of bacterial catheter-related sepsis. This treatment offers the advantage over current therapies of avoiding repeated catheter change and 2-6 weeks of systemic antibiotic therapy.

The results of this open multicenter trial with 100 patients of both sexes show that a single 300-mg dose of rosoxacin (Win 35,213) was effective in achieving a 94% cure rate, both clinical and bacteriological, on the seventh day after treatment in patients with uncomplicated acute gonococcal infection. The cure rate in men was 94% (86/92) and in women 100% (8/8). All isolates of Neisseria gonorrhoeae were susceptible to rosoxacin, as determined by 5-micrograms sensitivity disks. Adverse effects were seen in 14 patients--13 men and one woman. Twelve patients reported dizziness, one drowsiness, and one visual changes. It is concluded that rosoxacin can be of great usefulness in the epidemiological control of acute gonococcal infection, because of the lack of in vitro resistance to it, its minimal adverse effects, the low dose requirements, and the effectiveness of a single dose. The drug does not appear to have any treponemicidal action.