Quantitation of fragment X formation during thrombolytic therapy with streptokinase and tissue plasminogen activator.

We have determined the extent of fragment X formation during thrombolytic therapy by integration over time of the plasma fibrinopeptide B beta 1-42 concentration. This peptide is quantitatively released when fragment X is formed by plasmin action on fibrinogen or fibrin I. In response to streptokinase (SK) and rt-PA, 264 +/- 54 and 95 +/- 12 mg/dl respectively of fibrinogen was converted to fragment X. By immunoblotting, fragment X was demonstrated as early as 5 min after SK and 30 min after rt-PA, and was still evident 24 h after treatment. Patients treated with SK showed extensive further plasmin degradation of fragment X to fragments Y and D. Thus fragment X concentrations tend to be more similar in the two groups than would be expected from the extent of fibrinogen breakdown. Fragment X forms clots, but these have lower tensile strength and are more susceptible to further plasmin lysis than clots of fibrin. Thus the similar bleeding observed in the two treatment groups might be a reflection of their similar plasma fragment X concentrations.

Importance of balloon size in coronary angioplasty.

The effect of balloon size on the success of coronary angioplasty was studied to develop quantitative criteria for optimal selection of balloon size. Coronary dimensions of 165 stenotic lesions were measured by computer-assisted cinevideodensitometry in 120 patients who had undergone angioplasty with a balloon selected by visual estimates. Cross-sectional areas and diameters of normal and stenotic arterial segments were measured before and after angioplasty by a previously validated cinevideodensitometric technique. The diameter of the inflated balloon compared with that of the normal arterial segment was expressed as a ratio for sizing balloons. Oversized balloons with a ratio greater than 1.3 (n = 35) caused a high (37%) incidence of dissection, with three severely compromised arterial lumens. Undersized balloons with a ratio less than 0.9 (n = 29) often resulted in significant (greater than 50% diameter stenosis) residual stenotic lesions (21%) and a significantly (p less than 0.05) higher rate of repeat angioplasty for restenosis. Selection of balloon sizes with ratios in the 0.9 to 1.3 range (n = 101) resulted in a low (4%) incidence of dissection with few patients (3%) having significant residual stenosis. Mean residual stenosis (percent diameter reduction) was most severe for undersized (35.0 +/- 18%) or oversized (23.1 +/- 19%) balloons and least severe for balloons with a ratio of 0.9 to 1.3 (18.7 +/- 14%) (p less than 0.001). Repeat angioplasty for restenosis was more frequently required (p less than 0.05) for lesions dilated with undersized balloons. Thus, selection of angioplasty balloons that approximate or slightly exceed the diameter of the normal arterial diameter yields optimal angiographic results with minimal dissections and minimal residual stenotic lesions.

Thrombolysis in Myocardial Infarction (TIMI) Trial--phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase.

Two hundred ninety patients with acute myocardial infarction were treated according to random assignment with an intravenous infusion of either 80 mg of recombinant tissue plasminogen activator (rt-PA) over 3 h or 1.5 million units of streptokinase over 1 h. Patients received an intravenous bolus of heparin (5,000 U [USP]) before pretreatment coronary angiography and a continuous infusion (1,000 U/h) starting 3 h later. The frequency of major and minor hemorrhagic events (33% rt-PA, 31% streptokinase) and associated transfusions (22% rt-PA, 20% streptokinase) were comparable in both groups. More than 70% of bleeding episodes in each group occurred at catheterization or vascular puncture sites. Precipitable fibrinogen levels, measured in plasma samples collected in the presence of a protease inhibitor (aprotinin), declined in rt-PA and streptokinase groups by averages of 26 and 57% at 3 h and by 33 and 58% at 5 h, respectively (rt-PA versus streptokinase, p less than 0.001). At 5 h the plasma plasminogen declined by 57% (rt-PA) and 82% (streptokinase) (p less than 0.001); plasma fibrin(ogen) degradation products were higher in streptokinase-treated patients (244 +/- 12 micrograms/ml, mean +/- SE) than in rt-PA-treated patients (97 +/- 9 micrograms/ml, p less than 0.001). At 27 h, plasma fibrinogen and plasminogen levels were lower and fibrin(ogen) degradation products higher than pretreatment levels in both groups. The frequency of hemorrhagic events was higher in patients with greater changes in plasma factors at 5 h; within treatment groups the levels of fibrin(ogen) degradation products correlated with bleeding complications (p less than 0.005). Thus, in the doses administered, rt-PA induces systemic fibrinogenolysis that is substantially less intense than that induced by streptokinase. The high frequency of bleeding encountered is related to the protocol used, including vigorous anticoagulation, arterial punctures and thrombolytic therapy. These findings emphasize the need for avoidance of invasive procedures and for meticulous care in the selection and management of patients subjected to thrombolytic therapy.

Pleomorphic fibroma of the skin: a benign neoplasm with cytologic atypia. A clinicopathologic study of eight cases.

A clinicopathologic study of eight examples of polypoid and dome-shaped cutaneous fibrous lesions with sparse cellularity but striking nuclear atypia and rare mitotic figures is presented. Positive immunohistochemical staining for vimentin and actin supported the fibroblastic nature of these lesions. All eight cases were adults whose ages ranged from 33 to 67 years (mean 52 years). Five were women and three were men. Five lesions were located on extremities, two on the trunk, and one on the face and they measured from 4 to 16 mm in greatest dimension. The lesions were clinically followed from 4 months to 5 years. They all showed benign clinical behavior, with only one local recurrence in a lesion that had been incompletely removed. The nuclear atypia seen in these fibrous lesions may be similar to that which occurs in other benign mesenchymal neoplasms, such as pleomorphic lipoma, pleomorphic leiomyoma, ancient schwannoma, and variants of dermatofibroma with atypical cells. We suggest that "pleomorphic fibroma" is an appropriate term for this lesion based on its histologic differentiation, cytologic atypia, and benign clinical course.

Ocular melanoma.

Ocular melanomas are the most common intraocular malignancy in adults. The majority of ocular melanomas are choroidal melanomas. These tumors can be difficult to diagnose, especially when they are small. Documented growth of a lesion on serial examinations is the most important clinical feature favoring the diagnosis of a choroidal melanoma. Diagnostic studies including ultrasonography and angiography may be helpful in the diagnosis of these tumors. A number of treatment options are available for choroidal melanomas. These include photocoagulation, radiation therapy, local tumor resection, and enucleation.

Collagen biosynthesis in rabbit intraarticular patellar tendon transplants.

Autogenous patellar tendon grafts were transplanted into the knees of 40 New Zealand White adult rabbits. Grafts were subsequently analyzed for rate of collagen synthesis, collagen content, collagen type, histologic change, and cyanogen bromide cleavage patterns of collagen to closely assess the nature of collagen in tendon grafts up to 2 years from the time of transplantation. Tendon grafts were placed in rabbit knees as free fragments or were attached to synovium. These studies show that tendon grafts, even without vascularization or stress, remain viable after intraarticular transfer. Vascularization produces a trend toward increased collagen synthesis, but statistical analysis suggests that control levels of collagen synthesis continue after tendon transfers into rabbit knees. Cyanogen bromide cleavage peptides showed appropriate collagen formed by unstressed autogenous tendon transplants removed from rabbit knees up to 2 years from transplantation. All tendon grafts degenerated initially, but began to form histologically healthy looking connective tissue by 18 to 24 weeks after transplantation. Overall, the results are encouraging with regard to the fate of intraarticular tendon grafts.

Altered rheological properties of blood following administrations of tissue plasminogen activator and streptokinase in patients with acute myocardial infarction.

Tissue blood flow is determined by rheological properties of blood as well as by vascular resistance. In acute myocardial infarction patients who participated in the TIMI I trial, we compared the effects of recombinant tissue plasminogen activator (rt-PA) and streptokinase (SK) on blood rheological properties and plasma fibrinogen concentration. Blood viscosity was determined by using a coaxial cylinder viscometer at shear rates, gamma, of 0.01-200 sec-1. Red blood cell (RBC) deformability was studied by filtration through polycarbonate microsieves with pore size of 3 and 5 microns. Therapy with rt-PA resulted in slight decreases but statistically significant in blood viscosity from 5.2 +/- 0.5 to 4.9 +/- 0.4 cP (gamma = 52 sec-1), plasma viscosity from 1.36 +/- 0.09 to 1.32 +/- 0.06 cP, and plasma fibrinogen from 0.26 +/- 0.04 to 0.21 +/- 0.03 g/dl. SK therapy resulted in reductions in blood viscosity from 5.1 +/- 0.5 to 4.6 +/- 0.3 cP, plasma viscosity from 1.26 +/- 0.10 to 1.16 +/- 0.03 cP, and fibrinogen from 0.26 +/- 0.06 to 0.10 +/- 0.05 g/dl. Changes observed with SK were significantly greater than those observed with rt-PA (all p less than 0.05), and the differences persisted at 10 days after thrombolytic therapy. RBC deformability was similar in the two groups. The greater reduction of blood viscosity after SK than rt-PA suggests that, for a given degree of arterial patency, myocardial blood flow may be better maintained with SK than rt-PA in patients with acute myocardial infarction.

Using ICD-10 for case groups.

The definition of German case groups now uses an adaptation of the ICD-10: ICD-10-SGBV. For the transformation of the existing ICD-9-based definition into the ICD-10-SGBV an ICD-9/ICD-10 conversion table was used. The derived raw definitions were manually refined in detail. Due to the transformation of the classification system, the number of definitions increased immensely, as the ICD-10 SGBV is by far more detailed than the formerly used ICD-9. In our opinion, ICD-10 SGBV is not ideal for the definition of case groups, because this classification system is designed to support statistics on morbidity and mortality, but definitions of case groups are oriented to cost factors. Therefore the definition of case groups should be based on a specially designed classification system or one should reassess the necessity of a parallel definition by codes of classifications as well as by text. In both alternatives the introduction of a detailed and systematic medical documentation with expressive terminology systems will offer the advantage of classifying patients into medical oriented classifications as well as case groups.

Evaluation of rapid coagulase methods for the identification of Staphylococcus aureus.

Four rapid latex agglutination assays, StaphAurex (Wellcome Diagnostics, Research Triangle Park, N.C.), Bacto Staph (Difco Laboratories, Detroit, Mich.), SeroSTAT (Scott Laboratories, Inc., Fiskeville, R.I.), Veri-Staph (Zeus Technologies, Raritan, N.J.), and two hemagglutination tests, Staphyloslide (BBL Microbiology Systems, Cockeysville, Md.) and Hemastaph (Remel, Lenexa, Kans.), were compared with the conventional slide coagulase, tube coagulase (TC), and thermonuclease (TNase) tests for the identification of Staphylococcus aureus. A total of 118 clinical isolates of S. aureus (52 methicillin resistant), 50 S. epidermidis, 5 S. capitis, 2 S. hominis, 3 S. simulans, 6 S. saprophyticus, and 2 S. warneri were tested. The slide coagulase, TC and TNase tests detected 115 (97.5%), 117 (99.2%), and 118 (100%) of the S. aureus isolates, respectively. All showed 100% specificity. The StaphAurex, Veri-Staph, Staphyloslide, Hemastaph, SeroSTAT, and Bacto Staph assays correctly identified 117 (99.2%), 117 (99.2%), 116 (98.3%), 110 (93.2%), 108 (91.5%), and 107 (90.7%) of the S. aureus isolates, respectively. For methicillin-resistant S. aureus isolates, StaphAurex, Veri-Staph, Staphyloslide, Hemastaph, SeroSTAT, and Bacto Staph showed 1 (2%), 1 (2%), 2 (4%), 7 (13.5%), 7 (13.5%), and 8 (15.4%) false-negative results, respectively. All the commercial agglutination assays demonstrated false-positive results with strains of S. capitis, S. saprophyticus and S. warneri. The overall accuracy of the commercial agglutination assays compared with TC and TNase ranged from 90.7 to 99.2%. We recommend that negative reactions with the rapid commercial test kits for methicillin-resistant Staphylococcus isolates be confirmed with the TC or TNase test.

Type 1 diabetes mellitus associated with livedo reticularis: case report and review of the literature.

Livedo reticularis (LR) has been associated with numerous systemic diseases. Its relationship to diabetes mellitus (DM), however, has been poorly characterized. We report a case of LR in a 17-year-old with type 1 DM.

Midline medullary depressor responses are mediated by inhibition of RVLM sympathoexcitatory neurons in rats.

Mechanisms underlying the depressor and sympathoinhibitory responses evoked from the caudal medullary raphe (MR) region were investigated in pentobarbital sodium-anesthetized, paralyzed rats. Intermittent electrical stimulation (0.5 Hz, 0.5-ms pulses, 200 microA) of the MR elicited a mixed sympathetic response that consisted of a long-latency sympathoexcitatory (SE) peak (onset = 146 +/- 7 ms) superimposed on an inhibitory phase (onset = 59 +/- 10 ms). Chemical stimulation of the MR (glutamate; Glu) most frequently elicited depressor responses accompanied by inhibition of sympathetic nerve discharge. Occasionally, these responses were preceded by transient pressor and SE responses. We examined the influence of intermittent electrical stimulation (0.5 Hz, 0.5-ms pulses, 25-200 microA) and Glu stimulation of the MR on the discharge of rostral ventrolateral medulla (RVLM) premotor SE neurons. Peristimulus-time histograms of RVLM unit discharge featured a prominent inhibitory phase in response to MR stimulation (onset = 20 +/- 2 ms; duration = 42 +/- 4 ms; n = 12 units). Glu stimulation of the MR reduced blood pressure (-37 +/- 2 mmHg, n = 19) and inhibited the discharge of RVLM SE neurons (15 of 19 neurons). Depressor and sympathoinhibitory responses elicited by chemical and electrical stimulation of the MR region are mediated by inhibition of RVLM premotor SE neurons and withdrawal of sympathetic vasomotor discharge.

Application of intravascular brachytherapy: utilization of beta-irradiation source delivery systems within a community-based cardiac center.

PURPOSE: There are numerous clinical studies ongoing to assess the outcome, physics, and radiobiology of intravascular brachytherapy and its effect on the reduction of the rate of restenosis after balloon angioplasty procedures. The present study reports on the experience of two different delivery systems as utilized in the community hospital setting. METHODS AND MATERIALS: Patients were enrolled into one of four ongoing trials at our institution: the Novoste Beta-Cath trial, the Novoste Stents and Radiation Therapy trial (START), the Novoste START 40/20 trial, and the Guidant Intimal Hyperplasia Inhibition with Beta In-stent Trial (INHIBIT). The Novoste studies utilized the Novoste Beta-Cath System with 90Sr/Y, and the Guidant INHIBIT trial used 32P. Enrollments into the various trials were determined by inclusion and exclusion criteria specified by each protocol. Randomization was conducted per criteria as determined by the participating study protocol. RESULTS: Forty-two patients were enrolled in total. Thirty-four were included in the Novoste trials and eight in the Guidant study, according to availability of the trial. Assessment of practicality of treatment was dependent primarily on treatment duration and extension of time of catheterization procedures by the addition of intravascular radiation. Average dwell time within the Novoste trials was 3 min 40 s, and 7 min 46 s for patients in the Guidant study. No acute complications were observed in any of the trials. CONCLUSIONS: Intravascular brachytherapy can be performed in the community hospital setting without compromising the efficiency of balloon angioplasty procedures. Pending long-term outcome data and FDA approval for specific delivery systems, endovascular brachytherapy in community hospital cardiac catheterization laboratories can be realized in an efficient and timely manner.

Thrombolytic therapy with tissue plasminogen activator or streptokinase induces transient thrombin activity.

We have determined the plasma level of fibrinopeptide A as a specific index of thrombin activity during the infusion of a thrombolytic agent in patients with acute myocardial infarction. Peripheral venous plasma levels of fibrinopeptide A increased following the initiation of thrombolytic therapy from 2.7 nmol/L to a peak of 13.0 nmol/L at 30 minutes with streptokinase and from 1.1 nmol/L to a peak of 10.7 nmol/L at 90 minutes with tissue plasminogen activator. The amount of fibrinogen converted to fibrin I was determined by integration of the plasma level of fibrinopeptide A over time. The amount of fibrin I formed over the five-hour period from the start of drug infusion was approximately 10 mg/dL in response to either streptokinase or recombinant tissue plasminogen activator. We conclude that activation of coagulation occurs in response to thrombolytic therapy despite heparin administration. This thrombin action, though transient, would be sufficient to cause rethrombosis if localized and incompletely opposed by fibrinolytic activity.

Cinevideodensitometric analysis of the effect of coronary angioplasty on coronary stenotic dimensions.

The accuracy and reproducibility of caliper and cinevideodensitometric measurements of coronary stenotic dimensions were compared in radiographic phantom models and in coronary arteriograms of 28 patients undergoing coronary angioplasty. Projected, single-plane coronary cine frames were analyzed by a computer-assisted videodensitometric method, which measures stenotic cross-sectional area without assumptions about lesion geometry. The accuracy (2.4%) and precision (+/- 1.9%) of cinevideodensitometry for measuring percent area stenosis in Plexiglas models of eccentric stenotic lesions was superior to the accuracy (24.7%) and precision (+/- 5.4%) of caliper measurements. Interobserver variability was significantly (p less than 0.05) better for cinevideodensitometric (r = 0.98; SEE = 6.4%) than for caliper measurements (r = 0.87; SEE = 13.1%). After angioplasty, percent diameter stenosis measured by calipers fell from 70 +/- 12% to 30 +/- 15%. Mean percent area reduction measured by cinevideodensitometry fell from 89.1 +/- 8% to 40.1 +/- 22% and stenotic area increased five-fold, from 0.59 +/- 0.5 to 3.47 +/- 1.6 mm2. Pre and post PTCA gradients did not correlate with lesion dimensions. Cinevideodensitometric measurements of absolute stenotic dimensions were more reproducible than relative measurements expressed as a percentage, due to the tapered caliber of normal arterial segments. Thus, cinevideodensitometric measurements were more accurate and reproducible than caliper measurements. The angiographic effects of coronary angioplasty are best measured by cinevideodensitometry, because residual lesions post PTCA are often eccentric, have indistinct margins, and are better characterized by changes in area than by changes in diameter.

Ocular melanomas and melanocytic lesions of the eye.

This article describes several melanocytic lesions of the eye. Benign and malignant lesions will be discussed as well as a review of the dysplastic nevus syndrome and its proposed association with ocular melanoma. Ocular melanomas arise from the same embryologically derived melanocytes as their cutaneous counterparts. However, ocular and cutaneous melanomas differ in many respects. The diagnosis and management of these ocular tumors rely heavily on the ophthalmologist. However, knowledge of melanocytic lesions will aid the dermatologist in detection and in proper referral of these patients.

Automated peritoneal dialysis with 'on-line'-prepared bicarbonate-buffered dialysate: technique and first clinical experiences.

BACKGROUND: Automated peritoneal dialysis (APD) has the possibility of increasing the dialysis efficacy by using higher fill volumes, frequent dialysate exchanges, and tidal techniques. It is then possible to treat patients adequately without residual renal function. The drawbacks of the required high amounts of dialysis solution of up to 30 litres per session are the high costs of lactate-based dialysate bags and difficulties for the patients in handling these bags. So far, bicarbonate-based peritoneal dialysate, which may be more biocompatible, is only available for CAPD in double-chamber bags. In APD this could be overcome by 'on-line' preparation of bicarbonate-buffered dialysate using advanced technologies originally designed for on-line preparation of substitution fluid for haemofiltration. METHODS: Four patients without residual renal function were treated with APD five times weekly in a crossover study design. Patients received standard lactate-based (35 mmol/l) treatment (25 litres per session each) in weeks 1 and 3. In week 2 on-line-produced bicarbonate-buffered (37 mmol/l) dialysate was used. This dialysate was prepared by an AK 100 Ultra haemodialysis machine. The machine was modified for adding glucose from a 50% concentrate to the desired concentration of 1.7%. Electrolytes, pH, pCO2, and dialysis efficacy parameters were measured. Microbiological testing was carefully performed. RESULTS: Creatinine clearances, Kt/V, and pCO2 did not vary between the different treatment phases, whereas the pH showed a distinct increase during the bicarbonate phase. Repeated determinations of endotoxins and culturing showed no contamination of the dialysate. The composition of the produced dialysate was reproducible with respect to pH, pCO2, sodium, calcium and bicarbonate, whereas the glucose concentration varied by +/- 20%. CONCLUSIONS: On-line preparation of PD fluid with the AK 100 Ultra is easy and safe to handle. APD with dialysate containing 37 mmol/l bicarbonate provides improved acid base balance and possibly improved biocompatibility, and may lead to a significant cost reduction. Further development in order to provide smaller machines and more precise ways of achieving a desired dialysate glucose concentration is necessary.