Correlated strength in the nuclear spectral function.

We have carried out an (e,e'p) experiment at high momentum transfer and in parallel kinematics to measure the strength of the nuclear spectral function S(k,E) at high nucleon momenta k and large removal energies E. This strength is related to the presence of short-range and tensor correlations, and was known hitherto only indirectly and with considerable uncertainty from the lack of strength in the independent-particle region. This experiment locates by direct measurement the correlated strength predicted by theory.

Angular distributions for (3,4)(Lambda)H bound states in the (3,4)He(e,e(')K+) reaction.

The (3,4)(Lambda)H and (4)(Lambda)H hypernuclear bound states have been observed for the first time in kaon electroproduction on (3,4)He targets. The production cross sections have been determined at Q(2)=0.35 GeV2 and W=1.91 GeV. For either hypernucleus the nuclear form factor is determined by comparing the angular distribution of the (3,4)He(e,e(')K+)(3,4)(Lambda)H processes to the elementary cross section 1H(e,e K+)Lambda on the free proton, measured during the same experiment.

Measurement of the high energy two-body deuteron photodisintegration differential cross section.

The first measurements of the d(gamma,p)n differential cross section at forward angles and photon energies above 4 GeV were performed at the Thomas Jefferson National Accelerator Facility (JLab). The results indicate evidence of an angular dependent scaling threshold. Results at straight theta(cm) = 37 degrees are consistent with the constituent counting rules for E(gamma) greater, similar 4 GeV, while those at 70 degrees are consistent with the constituent counting rules for E(gamma) greater, similar 1.5 GeV.

Shiga toxin-induced tumor necrosis factor alpha expression: requirement for toxin enzymatic activity and monocyte protein kinase C and protein tyrosine kinases.

Infections with Shiga toxin (Stx)-producing bacteria cause bloody diarrhea which may progress to life-threatening complications, including acute renal failure and neurological abnormalities. The precise mechanism of disease progression is unclear, although evidence suggests that the localized production of the host proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 may exacerbate toxin-mediated vascular damage. Purified Stxs have been demonstrated to elicit proinflammatory cytokine synthesis from human peripheral blood mononuclear cells and monocytic cell lines in vitro. To understand toxin-monocyte interactions required for cytokine synthesis, we have treated differentiated THP-1 cells with purified wild-type toxins, enzymatic mutants, or B subunits and measured TNF-alpha production. Our data suggest that A subunit enzymatic activity is essential for cytokine production. THP-1 cells were treated with a series of protein kinase C (PKC), PKA, and protein tyrosine kinase inhibitors to examine the role of intracellular signaling molecules in Stx-mediated cytokine production. Treatment of cells with PKC and tyrosine kinase inhibitors blocked TNF-alpha secretion by Stx-stimulated THP-1 cells. Stx treatment directly activated PKC, which occurred at a point upstream of transcriptional activation of the gene encoding TNF-alpha.

Uptake of circulating insulin-like growth factor-I into the cerebrospinal fluid of normal and diabetic rats and normalization of IGF-II mRNA content in diabetic rat brain.

Brain injury has been prevented recently by systemic administration of human insulin-like growth factor-I (hIGF-I). It is widely believed that protein neurotrophic factors do not enter the brain from blood, and the mechanism by which circulating hIGF-I may be neuroprotective is uncertain. This investigation tested the hypothesis that hIGF-I is taken up into cerebrospinal fluid (CSF) from the circulation. (125)I-hIGF-I was injected subcutaneously into rats. The (125)I-IGF-I recovered from CSF and plasma were indistinguishable in size from authentic (125)I-hIGF-I on SDS-PAGE. An ELISA was used that detected immunoreactive hIGF-I, but not rat IGF-I, rat IGF-II, human IGF-II, or insulin. Osmotic minipumps were implanted for constant subcutaneous infusion of various hIGF-I doses. Uptake into CSF reached a plateau at plasma concentrations above approximately 150 ng/ml hIGF-I; the plateau was consistent with carrier-mediated uptake. The plasma, but not CSF, hIGF-I level was significantly reduced in streptozotocin diabetic vs. nondiabetic rats, and uptake of hIGF-I into CSF was nonlinear with respect to plasma hIGF-I concentrations. Nonlinear uptake excluded leakage or transmembrane diffusion of IGF-I from blood into CSF as a dominant route for entry, but the site and mechanism of uptake remain to be established. The IGF-II mRNA content per milligram brain (P < 0.02) as well as per poly(A)(+) RNA (P < 0.05) was significantly increased towards normal in diabetic rats treated by subcutaneous administration of hIGF-I vs. vehicle. This effect of circulating hIGF-I may have been due to regulation of IGF-II gene expression in the choroid plexus and leptomeninges, structures at least in part outside of the blood-central nervous system barrier. These data support the hypothesis that circulating IGF-I supports the brain indirectly through regulation of IGF-II gene expression as well as by uptake into the CSF.

Follow up of patients after valvular surgery: mail vs. telephone.

A study was undertaken to compare the results of patient follow up done by mail and by telephone. Using valve follow up questionnaires recently received by mail, 100 patients were randomly selected from this group for further follow up by telephone. Interviews were conducted while blinded to the mail response. Patients were questioned as to their functional status (NYHA), improvement as a result of surgery (IMP), incidence of reoperation (REOP) or bacterial endocarditis (SBE) and thromboembolic complications (TE). They were also asked whether they would prefer future follow up by mail or telephone. Analysis using the kappa coefficient and McNemar's test revealed a difference (p < 0.001) in NYHA when comparing mail and telephone responses but no difference in either IMP or TE. There was no incidence of REOP or SBE. Sixty-six percent of patients had no preference in type of future follow up and of the remaining 33%, two-thirds preferred to be contacted by phone. It appears that NYHA is significantly overestimated by the patient whereas the two methods of follow up are comparable when assessing IMP and TE. It should be noted, however, that patients seem to have difficulty in identifying the occurrence of TE and in differentiating between stroke and TIA.

Tricuspid valve replacement. Fifteen years of experience with mechanical prostheses and bioprostheses.

Tricuspid valve replacement is not a common operation. The purpose of this study was to examine the early and late results in 60 patients who underwent 28 (47%) bioprosthetic and 32 (53%) mechanical tricuspid valve replacements. All operations took place between January 1978 and June 1993 during which period a total of 4741 patients underwent valve replacement operation. Mean patient age was 50 +/- 15 (18 to 75) years. Forty-one patients (68%) were female and 19 patients (32%) were male. Forty-nine patients (82%) were in New York Heart Association class III or IV before operation. Forty-five patients (75%) were undergoing repeat cardiac valve operation. Seventeen patients (28%) had complex congenital cardiac problems. Operation was urgent in 15 patients (25%). The hospital mortality rate was 27% (16 patients). All patients with hospital death were in New York Heart Association class III or IV, were having repeat operations, or had complex congenital disease. Low output syndrome was observed in 21 patients (35%). Reoperation because of bleeding was required in seven patients (12%). Thirteen patients (22%) required permanent (epicardial lead) pacemaker implantation. Mean follow-up is 75 +/- 45 months (maximum 173 months) and 100% complete for the 44 patients who left the hospital. There have been 14 deaths (32%). Nine of these patients (64%) had mechanical valves and five (36%) had bioprostheses. Of the 11 cardiac deaths, three were valve related (bioprostheses). Three patients (10%) required reoperation because of tricuspid valve prosthetic failure (1 thrombosed mechanical valve, 2 failed porcine valves). Of the remaining 30 patients, 20 (67%) are in New York Heart Association class I or II. Seventeen patients have mechanical valves and 13 have bioprostheses. Twenty-six patients (90%) are receiving warfarin. Thromboembolism (transient ischemic attack) has occurred in one patient with a mechanical valve who also had a previous cerebrovascular accident. In this group there has been no hemorrhage, endocarditis, or new pacemaker requirement. Actuarial survival for the whole series is 37% +/- 9% and for the hospital survivors is 50% +/- 12% at 15 years. Linearized rates of valve-related complications are not different between groups. Tricuspid valve replacement is a beneficial procedure for patients with structural tricuspid valve disease, many of whom have other valvular or congenital disease. Contemporary mechanical prostheses and bioprostheses are equally effective in the tricuspid position. Mechanical valves should be considered for tricuspid replacement in young patients and in patients with mechanical valves implanted in the left side of the heart.

Vulnerability to ventricular arrhythmia: assessment by mapping of body surface potential.

It is now well established that the vulnerability of the ventricular myocardium to repetitive dysrhythm increases in the presence of greater than normal disparity local recovery times. Local recovery is reflected in the electrocardiographic waveform as an area of the ventricular deflection (QRST time integral), and thus disparate ventricular recovery may be manifested in the body surface distribution of this quality. To assess this possibility, we obtained simultaneous 120-lead electrocardiograms from both the anterior and posterior torso in 140 subjects (ages 8 to 75) grouped as follows: group A, 97 normal subjects; group B, 16 patients resuscitated from ventricular fibrillation or sustained ventricular tachycardia; and group C, 27 patients 6 to 12 months after myocardial infarction but without clinically significant arrhythmia. In each subject, the QRST integral was evaluated for each lead and isointegral contour maps were plotted. A score was assigned to each map, based on the number of extrema; each maximum or minimum scored one point, with the exception of simultaneously occurring anterior and posterior minima on the right shoulder (frequently occurring in normal subjects), which scored together only one point. All but one group A subject had dipolar QRST integral maps (mean +/- SD score 2.11 +/- 0.2). Conversely, 10 of 16 (62.5%) group B patients had scores of 3 or more (mean 3.16 +/- 1.08; p less than .01 vs group A). Group C patients had intermediate values, with eight of 27 (29.6%) scoring 3 or more (mean 2.46 +/- 83); this was less than in group B (p less than .01), but more (p less than .05) than in group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise electrocardiographic mapping in normal subjects.

To investigate the spectrum of change in multiple-lead exercise electrocardiograms, 120-lead body surface potential maps (BSPM) in normal adult subjects during upright, graded, submaximal exercise testing were recorded. Results showed that in the normal group, exercise was associated with substantial electrocardiographic changes on the body surface, many of which persisted during early recovery. The QRS waveform was minimally altered during exercise. Despite, however, no change in QRS duration, there was significant reduction in QRS potential range with consequent reduction QRS integral value. The ST waveforms changed markedly with exercise, showing abbreviated duration and increased slope. This was reflected by significantly increased ST potential range from rest to immediate cessation of exercise, which returned towards resting value during recovery. The effect of the altered ST-segment waveform was also reflected in torso potential distributions at two time instants during the ST-segment. When a spatially-fixed position on the ST-T waveform was evaluated (ST-segment offset), exercise resulted in small potential changes, especially over the torso area occupied by the standard V1 to V6 chest leads. However, when a temporally-fixed point (80 ms after QRS offset) was evaluated, there were large increases in potential over the precordium with exercise. Isointegral ST-segment maps, which reflect both spatial and temporal ST properties, showed that exercise was associated with substantial decreases in values over the precordium and inferior torso, and although diminished, they tended to persist through five minutes of recovery. Thus, electrocardiographic repolarization parameters are particularly affected by physiological exercise and, although the underlying causes of these changes remain undefined, they should be taken into account when evaluating the population at risk.