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Biomedical subjects

B Friedman

Publications and source records attributed to B Friedman.

At least 55 records · Page 3Linked to original sources
PubMed1995

BDNF and NT-4/5 exert neurotrophic influences on injured adult spinal motor neurons.

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.

Animals↗
PubMed1995

Positioning post-outpatient cardiac catheterization.

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.

Adult↗
PubMed1994

Pharmacokinetics and pharmacodynamics of multiple oral doses of MK-0591, a 5-lipoxygenase-activating protein inhibitor.

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.

5-Lipoxygenase-Activating Proteins↗
PubMed1994

Femoral venous catheters: a safe alternative for delivering parenteral alimentation.

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.

Catheterization, Peripheral↗
PubMed1994

Malignant thymoma. A complicated triad of SVC syndrome, cardiac tamponade, and DIC.

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.

Adult↗
PubMed1993

Appearance of granulocyte-macrophage colony-stimulating factor activity at allergen-challenged cutaneous late-phase reaction sites.

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)

Adolescent↗
PubMed1993

Mitral valve area calculations immediately after percutaneous balloon mitral valvuloplasty: effect of the atrial septal defect.

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.

Adult↗
PubMed1993

Biochemical activity, pharmacokinetics, and tolerability of MK-886, a leukotriene biosynthesis inhibitor, in humans.

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.

Administration, Oral↗
PubMed1993

Increased use of an expensive, elective procedure: total hip replacements in the 1980s.

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.

Adult↗
PubMed1993

Access to heart and liver transplantation in the late 1980s.

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.

Adult↗
PubMed1993

HMO medical directors' perceptions of geriatric practice in Medicare HMOs.

OBJECTIVE: To determine the extent to which health maintenance organizations (HMOs) with Medicare risk contracts utilize geriatricians and selected aspects of "organized" geriatric practice. DESIGN: A telephone interview survey. PARTICIPANTS: Eighty-two percent (64 of 78) of the HMOs with Medicare risk contracts as of June 1991. MEASUREMENTS: Questions to medical directors of the Medicare HMOs on (1) the presence of geriatricians, (2) the roles of geriatricians, and (3) "organized" geriatric practice. MAIN RESULTS: Fifty-three percent of the Medicare HMOs have one or more geriatricians, but only 19% have attempted to recruit geriatricians. Geriatricians provide primary care in 76% of the HMOs with geriatricians and serve as specialist consultants in 61%. Geriatricians are reported to be used actively in 32% of the HMOs that have them. The proportion of HMOs utilizing "organized" geriatric activities ranges from a high of 58% for a general health information questionnaire to a low of 12% for a special form(s) for comprehensive geriatric assessment. While the percentage of HMOs using each of the "organized" strategies is higher for the HMOs with geriatricians than for those without, this is statistically significant for only one strategy--the use of special approaches or formal protocols for problems frequently found in the elderly (P = 0.04). CONCLUSIONS: The perception of Medicare HMO medical directors is that about half of the HMOs utilize geriatricians and that there is evidence of "organized" geriatric practice. However, it appears that geriatricians and many of the elements of organized geriatric practice are used to a much lesser extent than experts recommend. Medicare HMOs must themselves test the various components of organized geriatric practice in order to determine their utility.

Aged↗
PubMed1993

Hospitals with chronic financial losses: what came next?

Hospitals with chronic losses might respond by closing, by drastically changing their services and patient mix, or by increasing efficiency. These possible responses are examined by studying a cohort of hospitals that were losing money between 1980 and 1984 as measured by their five-year average total revenue margins. These "negative-cohort" hospitals were followed through 1988 to see if they survived, and if they did, what changes they made. Only about 10 percent of hospitals in the negative cohort closed. The remainder did not alter their service mix or select in favor of easier, better-paying patients. However, there was a reduced rate of investment in new technologies.

Cohort Studies↗