A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty

Patients presenting within four hours of the onset of acute myocardial infarction were randomly assigned to receive 80 to 100 mg of recombinant human-tissue plasminogen activator (t-PA) intravenously over a period of three hours (n = 72) or placebo (n = 66). Administration of the study drug was followed by coronary arteriography, and candidates for percutaneous transluminal coronary angioplasty were randomly assigned either to undergo angioplasty on the third hospital day (n = 42) or not to undergo angioplasty during the 10-day study period (n = 43). The patency rates of the infarct-related arteries were 66 percent in the t-PA group and 24 percent in the placebo group. No fatal or intracerebral hemorrhages occurred, and episodes of bleeding requiring transfusion were observed in 7.6 percent of the placebo group and 9.8 percent of the t-PA group. As compared with the use of placebo, administration of t-PA was associated with a higher mean (+/- SEM) ejection fraction on the 10th hospital day (53.2 +/- 2.0 vs. 46.4 +/- 2.0 percent, P less than 0.02), an improved ejection fraction during the study period (+3.6 +/- 1.3 vs. -4.7 +/- 1.3 percentage points, P less than 0.0001), and a reduction in the prevalence of congestive heart failure from 33 to 14 percent (P less than 0.01). Angioplasty improved the response of the ejection fraction to exercise (+8.1 +/- 1.4 vs. +1.2 +/- 2.2 percentage points, P less than 0.02) and reduced the incidence of postinfarction angina from 19 to 5 percent (P less than 0.05), but did not influence the ejection fraction at rest. These data support an approach to the treatment of acute myocardial infarction that includes early intravenous administration of t-PA and deferred cardiac catheterization and coronary angioplasty.     

Family History of Hypertension and Cardiovascular Responses to Orthostatic Stress

Cardiovascular effects of orthostatic stress (sitting to standing) were assessed in 60 healthy young male subjects according lo family history of hypertension (half with a positive and half with a negative family history' of hypertension). Systolic (SBP) and diastolic blood pressure (DBF) were recorded on each successive heart heal using a non-invasive blood pressure tracking system. Heart rate (HR) and respiration rate (RR) were also recorded. During the postural change, characteristic phasic changes were shown with an initial fall and subsequent recover of SBP and DBF and a mirror image response in MR and RR. Phasic analysis of the pre-standing sit, peak/trough, and recovery stand values indicated group differences in the initial as well as the later phases of orthostatic response. In the initial phase, subjects with a positive family history of hypertension showed an earlier trough in systolic and pulse pressure and an earlier peak in heart rate response immediately on standing up. The level of the pulse pressure trough was also higher in these subjects. In the later standing phase, these subjects showed higher levels of pulse pressure. The results were interpreted in terms of increased sympathetic nervous system activity during the initial phase and structural and neurocirculatory abnormalities in the later phase of orthostatic regulation in individuals with a positive family history of hypertension.     

Transmission electron microscopic demonstration of vimentin in rat osteoblast and osteocyte cell bodies and processes using the immunogold technique

Background: The immunogold labeling technique and transmission electron microscopy were used to demonstrate the expression and position of the intermediate filament vimentin in rat osteoblast and osteocyte cell bodies and cell processes. Conventional light and transmission electron microscopic studies of bone cells demonstrated adjacent cell linkage to be mediated by osteoblast and osteocyte processes present within the canalicular system traversing the bone matrix. The cell processes were filled with densely packed filaments, many of which have been shown previously to be actin microfilaments. The appearance, however, of 10 nm diameter filaments in some cell processes and the fact that the intermediate filament vimentin has been defined in many cells of mesenchymal origin raised the possibility that some of these filaments might be vimentin. The ultrastructural colloidal gold immunochemical technique allowed for demonstration in situ of the expression of vimentin filaments plus accurate definition of their position. Methods: The studies were performed in newborn rat femoral and tibial diaphyseal cortical bone and in 1-week-old repair bone from 2.4 mm diameter defects made through the lateral cortex in 6-week-old rat femurs and tibias. The bone tissues for the immunochemical study were fixed in 1% glutaraldehyde, 4% paraformaldehyde, and 0.1 M phosphate buffer (pH 7.4) for 2 days. Decalcification was performed in 6% EDTA for 2–3 days. Infiltration involved use of Lowicryl resin K4M, and the embedding and curing processes were performed in a cryostat with temperatures ?30°C. An antivimentin monoclonal antibody was used for labeling using the postembedding technique. Effective antibody dilutions ranged from 1:10 to 1:200, with the dilutions of 1:25 and 1:100 showing the best combination of filament labeling with the least matrix background. The grids were exposed to 10 nanometer gold colloid conjugated goat anti-mouse IgM for demonstration of binding. Results: Vimentin immunolabeling was defined clearly in relation to filaments within the osteoblast and osteocyte cell body cytoplasm, throughout the entire length of the osteoblast and osteocyte cell processes, and in close relationship to the intercellular gap junctions which were present within the cell processes both close to the cell bodies and within the canaliculi well away from them. Conclusions: Immunogold labeling demonstrates the presence of the intermediate filament vimentin in osteoblast and osteocyte cell bodies and processes of rat bone. Vimentin distribution is not concentrated to specific areas, is present throughout the extent of the bodies and processes, and is seen immediately adjacent to gap junctions. © 1995 Wiley-Liss, Inc.     

An evaluation of the inactive mouse X chromosome in somatic cell hybrids

The expression of mouseZfx, Rps4, Ube1x, andXist was evaluated in hamstermouse somatic cell hybrids containing either an active or an inactive mouse X chromosome using polymerase chain reaction of reverse transcribed RNA (RT-PCR). The results showed thatZfx, Rps4, andUbe1x are expressed exclusively from the active mouse X, whileXist is expressed exclusively from the inactive X. These findings confirm the pattern of X inactivation for these mouse genes reported previously based on expression in somatic tissues of F₁ females from interspecific crosses. These results demonstrate the existence of differences between human and mouse X inactivation, as the corresponding human genes,ZFX, RPS4X, andUBE1 escape X inactivation.     

Virilism as a late manifestation in the Bardet-Biedl syndrome

The second case of virilism as a late manifestation of Bardet-Biedl syndrome (BBS) is described, with endocrine and histological evaluation. Both cases manifested ovulatory cycles and developed virilism in adulthood. Elevated plasma testosterone and 17-OH-progesterone were not suppressed by dexamethasone but were suppressed by medroxyprogesterone acetate. Peripheral and ovarian venous blood obtained at the time of surgery demonstrated a marked gradient for testosterone in both ovaries and for progesterone in the ovary bearing the corpus luteum. Histological evaluation of the ovaries demonstrated bilateral ovarian stromal hyperplasia with focal hyperthecosis. Bilateral ovariectomy resulted in complete correction of the endocrine abnormality, although the established hirsutism remains a mark of previous androgen excess.     

Differential Effects of Left versus Right Monaural Biofeedback for Heart Rate Increase

Cerebral lateralization in the voluntary increase of heart rate was investigated in a biofeedback experiment involving 20 right-handed female subjects randomly assigned to one of two groups: right or left ear input of stimulus and biofeedback information. The stimulus was a 1000 Hz tone which signalled the start and duration of 30 20-sec training trials. Feedback was a click presented every time an interbeat interval was shorter than a criterion established through a shaping schedule. A monetary bonus provided additional reinforcement at the end of each trial. Subjects given right ear feedback increased their heart rate significantly more than subjects given left ear feedback. The largest difference between the group means (7 bpm) was recorded after the first 20 training trials. The results are discussed in terms of hemispheric perceptual and functional differences.     

The role of IL-18 and IL-12 in the modulation of matrix metalloproteinases and their tissue inhibitors in monocytic cells

The matrix metalloproteinases (MMP) are enzymes crucial for the physiological patrol as well as pathological chemotaxis of immune cells to target tissues. The present study examined differential effects of pro-inflammatory [IL-18, IL-12 and tumor necrosis factor (TNF)-alpha] versus anti-inflammatory (IL-4) cytokines on the modulation of MMP and their endogenous tissue inhibitors (TIMP) expression in the U937 cell line. IL-18 and IL-12 separately and synergistically enhanced MMP-2, while TNF-alpha led to the elevation of MMP-9. All pro-inflammatory cytokines enhanced MT1-MMP expression and IL-4 suppressed TNF-alpha-induced MMP-9 expression. This study demonstrated that elevated IL-18 and IL-12, and related pro-inflammatory activity, may be associated with aberrant MMP activity, suggesting modulation of MMP expression using IL-12 and IL-18 antagonists as future therapeutic strategies to attenuate inflammatory and autoimmune disorders.     

The educational impact of ACGME limits on resident and fellow duty hours: a pre-post survey study.

PURPOSE: To assess the educational impact of Accreditation Council for Graduate Medical Education resident work-hour limits implemented in July 2003. METHOD: All trainees in all 76 accredited programs at two large teaching hospitals were surveyed between May and June 2003 (before work-hour reductions) and then between May and June 2004 (after work-hour reductions) about hours, education, and fatigue. Based on changes in weekly duty hours, 13 programs experiencing substantial reduction in hours were classified into a reduced-hours group. Differences in assessments of educational endpoints before and after policy implementation by trainees in the reduced-hours group were compared with those in other programs to control for potential temporal trends, using two-way ANOVA with interaction. RESULTS: The number of respondents was 1,770 (60% response rate). The reduced-hours group reported a significant decrease in time spent directly caring for patients (from 48.5 to 42.3 mean h/wk, P = 0.03), but the volume of important clinical experiences, including procedures, was preserved, as was the sense of clinical preparedness. On 22 questions related to educational quality and adequacy, only three differences in differences were significant, with the reduced-hours group reporting a relative increase in opportunities for research, decrease in quality of faculty teaching, and decrease in educational satisfaction. The percentage of trainees reporting frequent negative effects of fatigue dropped more in the reduced-hours programs than in the other programs (P < 0.05). CONCLUSION: This study shows that it may be possible to reduce residents' hours--and the perceived adverse impact of fatigue--while generally preserving the self-assessed quality, quantity, and outcomes of graduate medical education.