Low-energy electronic absorption of C60-
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Biomedical subjects
Publications and source records attributed to B Friedman.
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The purpose of this was to study evaluate the effects of interleukin-1 (IL-1) inhibition by human recombinant IL-1 receptor antagonist (IL-1ra) on plasma prostaglandin, leukotriene, and cytokine levels in sepsis syndrome. As part of a multisite, prospective, randomized, double-blind, placebo-controlled clinical trial, 19 septic patients received IL-1ra in a 100 mg bolus followed by 2.0 mg/kg/h i.v. for 72 h (n = 10) or placebo (n = 9). Plasma thromboxane B2 (TXB2), prostaglandin 6-keto-F1 alpha (PGI), leukotriene B4 (LTB4), leukotrienes C4D4E4 (LTC4D4E4), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF) were measured by ELISA before study drug infusion (baseline) and at 24, 48, 72, and 96 h after the beginning of the study drug infusion. Differences between placebo and IL-1-ra for plasma LTB4 and TNF were not significant. Plasma TXB2, PGI, LTC4D4E4, and IL-6, expressed as % baseline, were significantly lower in patients receiving IL-1ra than in the placebo group (p < .05), while plasma IL-1 was increased significantly. IL-1 may be a necessary mediator of increased circulating PGI, TXB2, LTC4D4E4, and IL-6 levels in patients with sepsis syndrome. Plasma IL-1 is increased with infusion of IL-1ra. The clinical significance of IL-1 in modifying circulating eicosanoid and cytokine concentrations in clinical sepsis is not clear from the data.
During 1980-87, eight hospitals in the Rochester, New York area participated in an experimental program to limit total revenue. This article analyzes: increase of costs for Rochester hospitals; trends for inputs and compensation; and cash flow margins. Real expense per case grew annually by about 3 percent less in Rochester. However, after 1984, Medicare prospective payment had an effect of similar size outside Rochester. Some capital inputs to hospital care were restrained, as were wages and particularly benefits. The program did not generally raise or stabilize hospital revenue margins, while the ratio of cash flow to debt trended down. Financial stringency of this program relative to alternatives may have contributed to its end.
OBJECTIVE: This research addresses the following types of responses by hospitals to increased financial risk: (a) increases in prices to privately insured patients (testing separately the effects of risk from the effects of "cost-shifting" that depends on level of Medicare payment in relation to case mix-adjusted cost); (b) changes in service mix offered and selectivity in acceptance of patients to reduce risk; and (c) efforts to reduce variation in resource use for those patients admitted. DATA SOURCES: The database includes a national panel of over 400 hospitals providing information from patient discharge abstracts, hospital financial reports, and county level information over the period 1980-1987. STUDY DESIGN: Econometric methods suitable to panel data are implemented, with tests for pooling, hospital-specific fixed effects, and possible problems of selection bias. PRINCIPAL FINDINGS: The prices paid by private insurers to a particular hospital were affected by the changes in risk imposed by Medicare prospective payment, the generosity of Medicare payment, state rate regulation, and ability of the hospital to bear risk. The risk-weighted measure of case mix did not respond to changes in payment policy, but other variables reflecting the management of care after admission to reduce risk did change in the predicted directions. CONCLUSIONS: Some of the findings in this article are relevant to current Medicare policies that involve risk-sharing, for instance, special allowances for "outlier" patients with unusually high cost, and for sole community hospitals. The first type of allowance appears successful in preserving access to care, while the second type is not well justified by the findings. State rate regulation programs were associated not only with lower hospital prices but also with less risk reduction behavior by hospitals. The design of regulation as a sort of risk-pooling arrangement across payers and hospitals may be attractive to hospitals and help explain their support for regulation is some states.
Adult motor neurons, like their immature antecedents, express the mRNA for the signaling receptor for brain-derived neurotrophic factor (BDNF) and for neurotrophin-4/5 (NT-4/5). However, while both BDNF and NT-4/5 support the survival of axotomized developing spinal motor neurons in vitro or in vivo, it is not known whether these factors continue to influence spinal motor neurons in adulthood. The present study tests if BDNF or NT-4/5 modulate the reactive responses of adult spinal motor neurons to nerve injury. We utilize sciatic nerve transection to axotomize the spinal motor neurons that form the retrodorsal lateral nucleus (RDLN) and show that, after axotomy, RDLN motor neurons lose ChAT immunoreactivity and also reexpress p75Ingfr, the low affinity receptor for all neurotrophin family members. Treatment with BDNF or NT-4/5 alters these effects of sciatic nerve transection. Both BDNF and NT-4/5 attenuate the loss of ChAT expression in axotomized RDLN motor neurons; thus, as compared to vehicle treatments, BDNF and NT-4/5 produce statistically significant increases in the optical density of ChAT immunostaining. Furthermore, BDNF and NT-4/5 also significantly increase the RDLN reexpression of p75Ingfr after sciatic nerve transection. Interestingly, essentially identical increases in RDLN ChAT and p75Ingfr immunostaining are produced by sciatic nerve crush injuries in the absence of exogenous neurotrophin treatment. These data show that treatment with exogenous BDNF and NT-4/5 changes the response of adult spinal motor neurons to sciatic nerve transection. Furthermore, these neurotrophins elicit reactive responses in axotomized motor neurons that mimic those produced by endogenous agents in regenerating crushed peripheral nerve.
UNLABELLED: The optimal positioning post-outpatient cardiac catheterization is a largely unexplored area of research. Traditionally, patients have been placed supine, with the head of the bed (HOB) flat. This study sought to explore the influence of three different post-procedure positions on the incidence of complications and patient perceptions of satisfaction. Sixty-nine patients were randomized into three groups immediately after hemostasis of the arterial puncture site was achieved. Group 1 patients were placed supine with the HOB flat. Group 2 patients were placed on their sides, with the affected extremity straight. Group 3 patients were placed on their backs, with the HOB at 15-30 degrees. Endpoints included the presence of any complication (bleeding, hematoma formation or expansion, back pain and urinary retention) and patient comfort and satisfaction with the randomized position. Patients were asked prior to discharge to select the position they would have preferred post-procedure. Selection of an alternative position was felt to indicate dissatisfaction with the randomized position. Ten patients in Group 1, and nine patients in Group 2 and Group 3 experienced a complication (X2 = 3.682, df = 1, p = 0.05). Eighty-five percent of Group 1 patients selected an alternative position vs. 24% of those patients in Group 2 and Group 3 (X2 = 27.6, df = 1, p < .001). CONCLUSION: varying patient position post-outpatient cardiac catheterization is at least as safe as the traditional supine position and is more comfortable for patients.
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The pharmacodynamics, kinetics, and tolerability of a new orally active 5-lipoxygenase inhibitor were evaluated in healthy male volunteers. MK-0591, 50, 125, and 250 mg every morning and 250 mg every 12 hours, was administered for 10 days. Leukotriene B4 biosynthesis ex vivo in ionophore (A23187)-stimulated whole blood and leukotriene E4 levels in urine were determined. Leukotriene B4 production was inhibited up to 90% of baseline for 12 hours after administration at the highest dose. The degree of leukotriene B4 inhibition ex vivo in whole blood significantly correlated with plasma MK-0591 concentrations (0 to 1500 ng/ml; r = 0.73). Urinary leukotriene E4 was inhibited by > 80% at 24 hours after administration for all dose levels. Pharmacokinetics of MK-0591 were linear, with a half-life of approximately 6 hours. Very little accumulation was seen after multiple dosing. MK-0591 had no effect on testosterone levels, and good tolerability was shown at all dose levels of MK-0591 administered for up to 10 days.
Femoral vein catheterization is an alternative method of obtaining central venous access. Placement of femoral venous catheters (FVCs) is possible in the majority of patients, suitable for most indications, and associated with a low complication rate during insertion. We wished to determine the incidence of infections or other complications resulting when parenteral nutrition was delivered through FVCs. Fifty-two patients were followed from a hospital-wide population including patients in the critical care units. Triple-lumen catheters were placed by using the sterile Seldinger technique, and sites were examined daily for inflammation. Bacteriologic surveillance was accomplished by submitting the catheter tip for semiquantitative cultures. If catheter line sepsis was suspected, blood samples for cultures were drawn through the catheter and peripherally. The rate of occurrence of colonized catheters was 9.6% (five of 52), and catheter sepsis was found in one case (1.9%). Other than inflammation at six (11.5%) of 52 catheter sites, noninfectious complications of FVCs were not found. On the basis of these findings, we consider FVC-delivered parenteral alimentation a safe and effective alternative to other forms of central venous access.
A patient presented with multisystem disease due to a very aggressive malignant thymoma. The case was complicated by the triad of cardiac tamponade, superior vena cava (SVC) syndrome, and disseminated intravascular coagulation (DIC). A review of the English literature reveals this to be a unique constellation of clinical symptoms and that DIC was heretofore unreported.
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The cytokines IL-3 and granulocyte-macrophage CSF (GM-CSF) activate and/or prime monocytes, basophils, and eosinophils for a number of proinflammatory events in vitro. It was hypothesized that IL-3 and GM-CSF might also participate in the local inflammatory cascades that occur at cutaneous blister sites after Ag challenge in vivo. The M-07e megakaryocytic leukemia cell line, which proliferates in response to IL-3 or GM-CSF, was used to determine whether these cytokines were present in fluids derived after Ag challenge in the cutaneous blister chamber model. Fluids from blister chambers after either Ag (timothy grass, orchard grass, or ragweed) or vehicle control challenge were collected hourly for 12 h from nine patients with allergic rhinitis. Cytokine (IL-3/GM-CSF) activity was modestly elevated at 4 h after Ag challenge compared to control with the median of maximal proliferation 4% (range, 2 to 22%) vs 2% (range, 1 to 14%), respectively (Ag vs control, p < 0.03). Activity peaked at 7 h (Ag = 10%, range 1 to 12%, vs control = 1%, range 1 to 9%, p < 0.02) and then steadily declined. No increase in cytokine activity over control was seen in Ag-challenged nonatopics (n = 5, p = NS), indicating that release did not result from a nonspecific effect of the Ag solution. Neutralization of cytokine bioactivity in pooled late phase reaction (LPR) fluids from h 4 to 12 (n = 5) with anti-IL-3, anti-GM-CSF, or both antisera revealed that the majority of the activity was GM-CSF. To better quantify cytokine levels, pooled LPR fluids prepared from an additional 11 subjects were concentration-dialyzed (10x) and tested for cytokine activity. Pooled fluids from Ag-challenged sites contained a median of 625 pg/ml (range, 30 to 1250 pg/ml) GM-CSF equivalents, whereas those from the vehicle control-challenged sites contained a median 30 pg/ml (range, 30 to 300 pg/ml) GM-CSF equivalents (p < 0.004 Ag vs control groups, n = 11). Concentrated fluid from Ag- and control-challenged sites in two nonatopic subjects contained < 10 pg/ml cytokine activity. To evaluate the IL-3 and GM-CSF activity with a separate technique, ELISA were performed on separately pooled blister fluids from six atopic subjects. Although no IL-3 activity was detected after Ag challenge in these six subjects, all of them demonstrated levels of GM-CSF at Ag-challenged sites comparable to that found in the bioassay.(ABSTRACT TRUNCATED AT 400 WORDS)
OBJECTIVES: The aim of this study was to assess the effect of the atrial septal defect on mitral valve area calculations after balloon mitral valvuloplasty. BACKGROUND: There is poor correlation between the hemodynamic-derived and Doppler mitral valve area immediately after mitral valvuloplasty. The reasons for this are unclear. METHODS: Twenty-five patients with severe mitral stenosis were studied. After balloon mitral valvuloplasty, serial mitral valve area calculations were performed with 1) the mitral dilating catheter across the atrial septum, 2) the 7F catheter across the atrial septum, and 3) with the atrial puncture site occluded with the balloon catheter. RESULTS: The mitral valve area determined by the Gorlin formula with balloon occlusion of the atrial septum was smaller than the mitral valve area determined without balloon occlusion (mean +/- SD 1.8 +/- 0.43 vs. 2.24 +/- 0.67 cm2, p < 0.005 for the mitral dilating catheter across the atrial septum and 1.8 +/- 0.43 vs. 2.19 +/- 0.52, p < 0.05 for the 7F catheter across the atrial septum). The mean of the differences between the mitral valve area derived by the Gorlin formula and by the Doppler pressure half-time method was smaller with the atrial septum occluded than when the dilating catheter or the 7F catheter was across the atrial septum (0.12 +/- 0.26 vs. 0.56 +/- 0.48 cm2 [p < 0.005] and 0.12 +/- 0.26 vs. 0.48 +/- 0.55 cm2 [p < 0.05]). Left to right shunting was detected less frequently by oximetry (60%), than by shunt ratios calculated by using the cardiac output measurements with and without balloon occlusion of the atrial septum (84%). CONCLUSIONS: The presence of left to right shunts after mitral valvuloplasty may account for some of the discrepancies between mitral valve area found at cardiac catheterization and that by the Doppler pressure half-time method; thus, the latter method may be reliably used to follow up patients in the long term.
MK-886, a leukotriene biosynthesis inhibitor, was evaluated in double-blind, placebo-controlled, randomized single- and multiple-dose studies in 12 and 24 healthy male subjects, respectively. The effects of a single dose (250, 500, and 750 mg) and multiple doses (100 mg and 250 mg every 8 hours) of MK-886 on calcium ionophore stimulated leukotriene B4 synthesis ex vivo in whole blood were evaluated. Inhibition of leukotriene B4 biosynthesis ex vivo occurred in a dose-related manner up to a 500 mg single dose, and 250 mg every 8 hours. A single dose of 500 mg MK-886 significantly inhibited leukotriene B4 biosynthesis by a maximum of 60% at 2 hours after the dose (p < 0.05). Multiple doses of 250 mg significantly inhibited leukotriene B4 biosynthesis by a maximum of 52% at 2 hours after the dose (p < 0.05). The degree of leukotriene B4 inhibition ex vivo in whole blood significantly correlated with plasma MK-886 concentrations (r = 0.78). In conclusion, the single and multiple doses of MK-886 evaluated in this study were well tolerated overall and partially inhibited leukotriene B4 biosynthesis ex vivo in whole blood.
Between 1980 and 1987, the number of hospital discharges with total hip replacement (THR) increased by more than 90%, while total hospital discharges fell by more than 10%. Total hip replacement is one of the most costly hospital inpatient procedures, both per case and in total Medicare expenses. Explanations for the growth in use of THR may clarify some of the major forces driving national health care costs. This study assumes that treatment choices are made by (or for) each patient to maximize expected net benefits. Within this framework, the use of THR might have increased because of improved safety for the procedure, longer life expectancy and better control of many serious illnesses that led to increased demand for quality-enhancing procedures, and increased out-of-pocket cost for alternative treatments that are not covered well by insurance. These possible explanations imply changes in the characteristics of THR recipients over time. An upward shift was found in the age distribution of patients, more than simply because of an aging of the population. Sharply increased proportions of patients were also found with serious comorbidities such as cancer and dementia. The safety of the procedure seems to have improved, in terms of the death rate in the hospital. The results suggest that demands for expensive, elective procedures have been increasing for patients previously regarded as too old or impaired to benefit sufficiently. This process leads to continuing increases in real health care expenses even without the invention of new technologies.
Because of a shortage of usable organs, many who require heart or liver transplants for survival will not have access to them. Access to care may reflect demographic factors and ability to pay, as well as medical considerations. Receipt of an organ may be influenced by expected survival with and without a transplant, age, gender, race, ability to pay, and distance to a transplant center. Discharge abstract data from a national sample of over 500 hospitals in 1986 and 1987 were used to select heart and liver recipients and others with end-stage diseases who did not receive a transplant. Multivariate logistic regression analyses were then used to estimate how receipt of a transplant was influenced by expected years of survival after transplantation (YAT), expected ability to pay, age, sex, race, and distance to a transplant center. Controlling for differences in expected YAT, age, sex, race, and distance to the transplant center, those expected to have the most ability to pay were more likely to receive heart and liver transplants, compared to those expected to have medium ability to pay. Third-party coverage was particularly important in receipt of a transplant for those with absolute contraindications. Expected YAT and age were significant, with some evidence of a tradeoff between urgency and expected YAT in the case of hearts. Men were more likely to obtain heart transplants and women were more likely to get liver transplants. The effects of distance were small. Existing regulatory incentives and biological, medical, and cultural reasons may justify the age-, sex-, race-, and prognosis-related differences in the odds of receiving a transplant. The importance of ability to pay may not have been adequately observed in previous studies restricted to the patients screened at major transplant centers. Hospital discharge records with personal identifiers, linkage to official waiting lists, and better patient level socioeconomic information would permit more definitive analysis.