PubMed Health⌕ Search

Biomedical subjects

Y Friedman

Publications and source records attributed to Y Friedman.

At least 19 recordsLinked to original sources
PubMed2002

Regional decreases in NK-3, but not NK-1 tachykinin receptor binding in dystonic hamster (dt(sz)) brains.

Although the pathophysiology of primary dystonias is currently unknown, it is thought to involve changes in the basal ganglia-thalamus-cortex circuit, particularly activity imbalances between direct and indirect striatal pathways. Substance P, a member of the tachykinin family of neuropeptides, is a major component in the direct pathway from striatum to basal ganglia output nuclei. In the present study quantitative autoradiography was used to examine changes in neurokinin-1 (NK-1) and neurokinin-3 (NK-3) receptors in mutant dystonic hamsters (dt(sz)), a well characterized model of paroxysmal dystonia. NK-1 receptors were labeled in 10 dystonic brains and 10 age-matched controls with 3 nM [(3)H]-[Sar(9), Met(O(2))(11)]-SP. NK-3 binding sites were labeled in adjacent sections with 2.5 nM [(3)H]senktide. NK-1 binding was found to be unaltered in 27 brain areas examined. In contrast, NK-3 binding was significantly reduced in layers 4 and 5 of the prefrontal (-46%), anterior cingulate (-42%) and parietal (-45%) cortices, ventromedial thalamus (-42%) and substantia nigra pars compacta (-36%) in dystonic brains compared to controls. The latter effects may be particularly relevant in view of evidence that activation of NK-3 receptors on dopaminergic neurons in the substantia nigra pars compacta can increase nigrostriatal dopaminergic activity. Since previous studies indicated that a reduced basal ganglia output in mutant hamsters is based on an overactivity of the direct pathway which also innervates substantia nigra pars compacta neurons, the decreased NK-3 binding could be related to a receptor down-regulation. The present finding of decreased NK-3 receptor density in the substantia nigra pars compacta, thalamic and cortical areas substantiates the hypothesis that disturbances of the basal ganglia-thalamus-cortex circuit play a critical role in the pathogenesis of paroxysmal dystonia.

Animals↗
PubMed2001

Ethical issues in the critically ill patient.

Ethical issues have emerged in recent years as a significant component of care in the critically ill patient. Recently, the primary emphasis has been directed to care at the end-of-life. The factor that has been identified as the most important to patients and families and the one that is accomplished the least often is successful communication with the physicians. When communication does not take place or is inadequate physicians are left to try to determine what their patient's wishes would have been regarding end-of-life decisions. This leads to tremendous potential for conflict between the physician and the family, as the patients are often incapable of participating in any discussion regarding end-of-life care. Advance planning on the part of the patient in terms of making their wishes known and education of the health care professionals is essential in promoting effective communication, thereby avoiding conflict in these difficult end-of-life decisions.

Advance Directives↗
PubMed1999

Acute stress increases thyroid hormone levels in rat brain.

BACKGROUND: In experimental animals, exposure to uncontrollable stress induces a number of behavioral and biochemical changes that resemble symptoms seen in human depression and other psychiatric conditions. The present study used a yoked design to examine the effects of uncontrollable footshock stress on brain thyroid hormones in male and female rats. METHODS: Animals in one group received 15 trials where footshock could be terminated by pressing a lever (escapable shock). Rats in a second group received the same amount of shock, but had no control over shock termination (inescapable shock). Control rats received no shock. RESULTS: No significant differences were found among the three groups, for either males or females, in whole brain levels of thyroxine (T4) 3 hours after the footshock session. In contrast, significant group differences in brain levels of triiodothyronine (T3) were found for both males and females. In males, brain T3 was elevated by 21% in the inescapable shock group when compared to controls (p < .012). In females, brain T3 increased by 19% in the escapable shock group when compared to controls (p < .026). Plasma levels of both T3 and T4 were at control levels for all groups. CONCLUSIONS: These results provide the first demonstration that brain T3 levels change rapidly in response to acute stress. The data further suggest that the effects of stress controllability on brain T3 levels may be different for males and females.

Acute Disease↗
PubMed1996

Characterization of a short unique sequence in the yeast HO gene promoter that regulates HO transcription in a SIN1 dependent manner.

Recently it has become clear that general chromatin proteins as well as sequence-specific DNA binding proteins are important in the control of gene expression. SIN1 in Saccharomyces cerevisiae is a chromatin component that regulates the transcription of a family of genes. Previously, we identified a 32 bp unique sequence (here termed XBS) in the promoter of one of those genes, HO, which specifically binds a protein that interacts with SIN1. We also found that this sequence can function as a weak UAS in a heterologous promoter that is dependent on the presence of SIN1. Here we report a relationship between the level of HO expression and the presence of the short sequence in situ in the HO gene. By comparing the expression of HO from wild type or XBS deleted HO promoters, we concluded that XBS serves as a weak UAS in situ in the HO gene, that it influences HO transcription via the SWI/SNF complex, and that sequences other than the XBS mediate the effect of SIN1 on HO transcription. In addition, we show that a portion of the SIN1 protein that has sequence similarity to mammalian HMG1 preferentially binds the XBS.

Base Sequence↗
PubMed1996

Nitrous oxide depresses spinal F waves in rats.

BACKGROUND: Evoked, recurrent electromyographic activity (F waves) reflect alpha-motor neuron excitability. Based on observations that other inhaled anesthetics do so, we hypothesized that nitrous oxide, alone or in combination with isoflurane, would depress F-wave activity and correlate with depression of movement response to tail clamp or electric stimulation. METHODS: In study 1, the authors examined the effect of nitrous oxide in combination with isoflurane in 13 normocapnic Sprague-Dawley rats anesthetized with 1.0% isoflurane (0.7 minimum alveolar concentration) in oxygen. The tibial nerve was stimulated at the popliteal fossa, and evoked electromyographic activity [M (direct neuromuscular junctional response) and F waves] were recorded from ipsilateral foot muscles. The effect of the addition of 30% or 70% nitrous oxide was measured. F-wave amplitude/M-wave amplitude ratio (F/M) was determined from each stimulus-electromyographic response pair. F/M vs. movement response to 60-s tail clamp was assessed after each recording session. F-wave amplitude/M-wave amplitude ratio at adjacent doses that permitted and prevented movement were compared. In study 2, the authors examined the effect of (hyperbaric) nitrous oxide as the sole anesthetic agent on F waves. In 11 rats anesthetized with isoflurane, stimulation and recording electrodes were placed as described above, with additional electrodes for stimulation placed in the tail. Rats were placed in a pressure chamber pressurized with nitrous oxide/oxygen to 3.4 atm. Thirty m were allowed for isoflurane washout. Electromyographic activity was evoked and recorded at 1.0, 1.6, 2.2 and 2.7 atm N2O (random order). Movement in response to 60 s of 15 V, 50-Hz tail stimulation was evaluated after each recording session. RESULTS: Nitrous oxide with or without isoflurane produced a dose-dependent decrease in F/M. By interpolation of this data, the authors found that 2 atm N2O alone, or 44% N2O added to 1.0% isoflurane at 1.0 atm, produced 1.0 minimum alveolar concentration anesthesia. At the deepest level of isoflurane/ nitrous oxide that permitted movement, mean F/M was 20.6 +/- 17.5%; at the lowest concentration that blocked movement, rats had a mean F/M of 13.7 +/- 13.9% (P = 0.01). At the minimal hyperbaric nitrous oxide blocking movement, rats had a mean F/M of 3.7 +/- 2.9%, whereas the F/M at the highest nitrous oxide dose that permitted movement was 4.4 +/- 2.7% (P < 0.04). CONCLUSIONS: Because nitrous oxide depressed F-wave but not M-wave activity, the data suggest a central (spinal) rather than neuromuscular junctional site of action of this agent. The direct correlation between nitrous oxide dose, F-wave amplitude depression, and surgical immobility suggests the possibility of using F-wave activity to predict the likelihood of anesthetic-induced immobility. However, the mechanism of action of nitrous oxide may differ from that of the potent inhaled agents.

Anesthetics, Inhalation↗
PubMed1996

Comparison of percutaneous and surgical tracheostomies.

OBJECTIVE: To compare the safety and efficacy of percutaneous dilational tracheostomy (PDT) with surgical tracheostomy (ST). DESIGN: Prospective randomized trial. SETTING: Public urban teaching hospital. PATIENTS: Twenty-six patients were randomized to undergo PDT and 27 patients to ST. RESULTS: The time from randomization into the study until tracheostomy was performed was 28.5 +/- 27.9 h in the PDT group and 100.4 +/- 95.0 h in the ST group (p < 0.001). PDT was performed in 8.2 +/- 4.9 min vs 33.9 +/- 14.0 min for ST (p < 0.0001). There was no significant difference in intraprocedural complications between the groups. Postprocedural complication rates were 12% for PDT and 41% for ST (p = 0.008). CONCLUSION: PDT is superior to ST logistically. PDT can be performed at the bedside eliminating the risk of patient transport. Because operating room scheduling is not necessary, PDT can be performed earlier once the decision to do a tracheostomy is made, which will improve ICU utilization. PDT is a faster procedure to perform and has fewer postprocedural complications.

Female↗
PubMed1995

A method for monitoring the glycosylation of recombinant glycoproteins from conditioned medium, using fluorophore-assisted carbohydrate electrophoresis.

We have developed a method for monitoring the N-glycosylation of recombinant glycoproteins directly from conditioned medium samples. Proteins in the conditioned medium are separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotted onto polyvinylidene fluoride membranes. After staining the membranes with Coomassie blue, the protein(s) of interest is excised. Oligosaccharides are released from the membrane-bound glycoprotein by digesting with peptide N4-(acetyl-beta-glucosaminyl) asparagine amidase and labeled with the fluorophore 8-aminonaphthalene-1,3,6-trisulfonate (ANTS). Labeled oligosaccharides are then separated on polyacrylamide gels which allow for the direct comparison of samples. We have shown that recombinant human lysosomal hydrolase alpha-galactosidase A is N-glycosylated with both sialylated and phosphorylated oligosaccharides. ANTS-labeled oligosaccharide bands from alpha-galactosidase A were isolated from polyacrylamide gels. Sialylated and phosphorylated bands were identified by shifts in their electrophoretic mobility after digesting with neuraminidase or alkaline phosphatase to remove sialic acid or phosphate groups, respectively. Using the ANTS-labeled oligosaccharides from alpha-galactosidase A, we have shown that polyacrylamide gels can be used to resolve sialylated and phosphorylated oligosaccharide structures.

Amidohydrolases↗
PubMed1995

Improving long-term prognosis for survivors of mechanical ventilation in patients with AIDS with PCP and acute respiratory failure. Five-year follow-up of intensive care unit discharges.

BACKGROUND: Before 1987, the hospital survival of patients with acquired immunodeficiency syndrome, Pneumocystis carinii pneumonia, and acute respiratory failure receiving mechanical ventilation was less than 15%. Hospital survival has improved since then, but concerns have been raised that the post-hospital discharge survival of these patients remains extremely poor. This study evaluated the long-term survival of patients discharged alive after an acute episode of acute respiratory failure caused by P carinii pneumonia. METHODS: A prospective cohort study was conducted for the 5-year period from May 1987 through May 1992 in an urban teaching hospital. Forty-seven patients discharged from the hospital after receiving mechanical ventilation and/or continuous positive airway pressure for acquired immunodeficiency syndrome, P carinii pneumonia, and acute respiratory failure were followed up from their initial intensive care unit admission until death or termination of the study to measure the long-term survival and cumulative probability of survival of the study cohort. Actuarial life-table analysis was performed, and long-term cumulative probability of survival was calculated on the basis of the life-table analysis. Median survival was estimated by means of the product-limit method. RESULTS: During the 5-year follow-up of the 47 subjects, 31 patients died, 12 were unavailable for follow-up, and four were still alive at the end of the cutoff. The cumulative survival rate at 1 year was 80% (95% confidence interval, 92% to 68%); at 2 years, 49% (95% confidence interval, 65% to 34%); at 3 years, 18% (95% confidence interval, 32% to 4%); and at 4 years, 6% (95% confidence interval, 17% to 0%). Median survival time for all subjects was 602 days (1.65 years), and the longest survival time for a single patient was 1774 days (4.86 years). CONCLUSIONS: Post-hospital discharge survival of patients with acquired immunodeficiency syndrome, P carinii pneumonia, and acute respiratory failure has improved dramatically in the past decade. Patients can undergo intubation and mechanical ventilation with the hope of reasonable long-term survival.

AIDS-Related Opportunistic Infections↗
PubMed1994

Prognosis of early versus late ventricular fibrillation complicating acute myocardial infarction.

Earlier studies have suggested that patients exhibiting late (> 24 h) ventricular fibrillation during acute myocardial infarction had a poorer outcome in comparison to myocardial infarction patients with early (< 24 h) ventricular fibrillation. Between August 1981 and July 1983, 5839 consecutive patients with acute myocardial infarction were hospitalized in 13 out of 21 operating coronary care units in Israel. Demographic and medical data were collected from hospitalization charts and during 1 year of follow-up. Mortality assessment was done for 99% of hospital survivors up to mid-1988 (mean, 5.5 years). The incidence of ventricular fibrillation in the SPRINT Registry was 6% (371/5839). Patients with ventricular fibrillation in the setting of cardiogenic shock (n = 107) were excluded from analysis. Patients with late ventricular fibrillation (n = 109; 41%) were older and had a more complicated hospital course than patients with early ventricular fibrillation (n = 155; 59%). In-hospital and 1-year post-discharge mortality were significantly higher in patients with late ventricular fibrillation (63% and 17%) as compared to patients with early ventricular fibrillation (26% and 4%, respectively; P < 0.05 for each). This difference vanished 5 years after hospital discharge. After multiple logistic regression analysis late occurrence of ventricular fibrillation emerged as an independent predictor of increased in-hospital mortality (Odds ratio, 4.29; 95% confidence interval, 2.11-8.74) but not for subsequent death. Patients with late ventricular fibrillation during the hospital course of acute myocardial infarction had a poorer immediate and subsequent outcome in comparison to patients with early ventricular fibrillation.

Aged↗
PubMed1993

Immediate and long-term prognostic significance of a first anterior versus first inferior wall Q-wave acute myocardial infarction. Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) Study Group.

Of 3,981 patients with a first Q-wave acute myocardial infarction (AMI), 1,929 (48%) had an anterior and 1,724 (43%) an inferior wall AMI. These 2 groups were well-matched with respect to age, gender and relevant history. The in-hospital mortality rate was 18%, and the 1- and 5-year post-discharge mortality rates were 9 and 25%, respectively, in patients with anterior wall AMI compared with the corresponding rates of 11, 6 and 19% in those with inferior wall AMI (p < 0.0001 for each category). The frequency of recurrent nonfatal AMI in the year after the index AMI was 8% in the patients with anterior wall AMI compared with 4% in those with inferior wall AMI (p < 0.0001). By multiple logistic regression analysis of events, anterior wall AMI was an independent predictor of in-hospital mortality only. The findings indicate that the anatomic location of a Q-wave AMI influences immediate and short-term survival of patients with a first Q-wave AMI.

Aged↗
PubMed1993

Frequency and prognostic significance of secondary ventricular fibrillation complicating acute myocardial infarction. SPRINT Study Group.

The incidence of secondary ventricular fibrillation (VF) complicating acute myocardial infarction (AMI) was 2.4% in a large cohort of unselected patients with AMI (142 of 5,839). Secondary VF was more frequent in patients with recurrent AMI (4%) than in those with a first AMI (1.9%) (p < 0.01). The hospital course was more complicated and in-hospital mortality was significantly higher in patients with secondary VF than in those with the same clinical hemodynamic condition but without VF (56 vs 16%; p < 0.0001). Multivariate analyses confirmed secondary VF complicating AMI as an independent predictor of high in-hospital mortality, with an odds ratio of 7 (95% confidence interval 4.6-10.6). However, long-term mortality after discharge (mean follow-up 5.5 years) was not increased in patients with as compared with those without secondary VF (39 vs 42%). These findings were also true when patients receiving beta blockers and antiarrhythmic therapy were excluded from analysis. Thus, this life-threatening arrhythmia occurring during hospitalization is not a marker of recurrent susceptibility to VF or an indicator of increased mortality after discharge from the hospital.

Aged↗