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Biomedical subjects

M Weiner

Publications and source records attributed to M Weiner.

At least 127 records · Page 7Linked to original sources

Clinical, blood gas, and lactate changes in the course of the treatment of peripheral vascular disease with a hemodialysate.

In a double-blind comparison with placebo, treatment with a hemodialysate (Solcoseryl) in severe peripheral vascular disease (PVD) resulted in a distinct improvement in symptomatology and clinically observed pathology. Initially depressed ApO2 was normalized with a corresponding increase in AO2 saturation, an increase in A-V pO2 difference, and reduction of elevated blood lactate levels. Correction of disturbed O2 diffusion is postulated to explain these observations. The mechanism proposed may be operative in lung-to-blood, blood-to-tissue, within-tissue and within-cell aspects of oxygen transport under pathologic conditions.

Actihaemyl↗

Stimulation SFEMG in myasthenia gravis.

The diagnostic usefulness of single-fiber electromyography (SFEMG) in the diagnosis of neuromuscular transmission disorders is well established. Increased jitter is one of the earliest indications of abnormality. In patients with severe weakness, tremor, or altered consciousness, performance of the study is difficult because of the degree of cooperation needed. We studied five patients and eight normal subjects with voluntary and stimulation SFEMG techniques. Our results, in search of normal values and changes with pathology, revealed differences in the values of jitter and the percentage of abnormal fibers between both techniques. The mean consecutive difference (MCD) is smaller (on average 30% less), and the percentage of abnormal fibers is lower (on average 10% less) with the stimulation technique. These differences are largely explained by the jitter measurement of one endplate with the stimulation technique versus two endplates with the voluntary. They may also be related, however, to the difference in motor unit populations sampled with each technique.

Aged↗

A descriptive analysis of emergency visits to an inner city family practice center.

A six-month prospective study of daily emergency visits was performed at an inner city family practice center in order to understand the utilization pattern of emergency services. 487 visits were identified during the study period. In general, patients of junior residents made more visits. The majority of visits (97%) were nonemergent. The most common presenting complaint was a general symptom (17%), although the most frequent diagnosis was in the supplementary category (17%) that includes medication renewals, the completion of forms and maternal and child health care. Females, the unemployed, the elderly, and individuals with poverty levels of income were most frequently seen in the emergency setting. The reasons for these patterns and the need for further investigations in this area are discussed.

Community Health Centers↗

High-dose naloxone in tardive dyskinesia.

Tardive dyskinesia (TD) is thought to result from nigrostriatal dopaminergic supersensitivity secondary to prolonged neuroleptic exposure. Preclinical studies have demonstrated that the opiate antagonist naloxone can acutely reverse a haloperidol-induced hyperdopaminergic state. In a trial of high-dose naloxone, 20 patients with TD received i.v. naloxone (20 mg, 40 mg, and placebo) under double-blind conditions. At baseline and at regular postdrug intervals, patients were evaluated using a battery of motor, clinical, and neuropsychological measures to study effects on neurological, behavioral, and cognitive functions. There was a significant improvement in involuntary movements at 30 min postnaloxone, together with improvement in clinical ratings at that time point, as well as some cognitive changes. The implications of these findings for the putative functional relationship between dopaminergic and enkephalinergic systems in the nigrostriatal area are discussed.

Adult↗

The 24-hour posttransfusion survival and lifespan of autologous baboon red cells treated with inositol hexaphosphate-polyethylene glycol or inositol hexaphosphate-adenosine triphosphate-polyethylene glycol to decrease oxygen affinity.

Baboon red cells were treated to reduce oxygen affinity by an osmotic-pulse procedure using dimethyl-sulfoxide. Inositol hexaphosphate (IHP) alone or IHP and adenosine triphosphate (ATP) were incorporated into the red cells in the presence of polyethylene glycol (PEG). The procedure produced variable increases in the red cell P50 value, i.e., the partial pressure of oxygen at which 50% of the hemoglobin was saturated. The effect of treatment of autologous baboon red cells on the 24-hour posttransfusion survival value and lifespan T50 value was measured using a double-label procedure. The data demonstrate that the increase in the P50 value of treated red cells was negatively correlated with the 24-hour posttransfusion survival value; the higher the P50 value, the poorer the 24-hour posttransfusion survival value. The 24-hour posttransfusion survival value for nontreated baboon red cells was 90% and the T50 value was 14 days. The IHP-ATP-PEG-treated red cells had significantly higher red cell ATP levels than did IHP-PEG-treated red cells. The 24-hour posttransfusion survival value was 68% for the IHP-ATP-PEG treated red cells and 52% for the IHP-PEG-treated red cells when the increase in P50 ranged from 10 to 20 mm Hg; the lifespan T50 value for both the IHP-ATP-PEG-treated red cells and the IHP-PEG-treated red cells was 15 days. Osmotic pulse treatment produced significant red cell injury manifested by the 24-hour posttransfusion survival value. However, modification of the RBC with IHP-PEG or IHP-ATP-PEG to decrease hemoglobin affinity for oxygen did not affect their lifespan.

Adenosine Triphosphate↗

Effects of release factor context at UAA codons in Escherichia coli.

In Escherichia coli, nonsense suppression at UAA codons is governed by the competition between a suppressor tRNA and the translational release factors RF1 and RF2. We have employed plasmids carrying the genes for RF1 and RF2 to measure release factor preference at UAA codons at 13 different sites in the lacI gene. We show here that the activity of RF1 and RF2 varies according to messenger context. RF1 is favored at UAA codons which are efficiently suppressed. RF2 is preferred at poorly suppressed sites.

Bacterial Proteins↗

Directed drug distribution: adding controlled brain activity to a drug.

Environmental factors can alter the state of an organism so as to influence the response to drugs. This fact is widely recognized even though the responsible mechanisms are difficult to understand and control. The capacity of environmental influences to alter local drug pharmacokinetics is rarely considered. Drug localization and resulting action within the brain are influenced by vascular blood flow factors, local concentration differences in competing neurohumours, and receptor density. These are all frequently asymmetrically represented in the brain and drug effects are correspondingly laterality dependent. Attention to regional brain pharmacokinetics and the influence of environment on regional blood flow, local neurohumor concentration, and receptor density represents an untapped opportunity to enhance the desired effect of a centrally active drug at its site of action without enhancing general systemic toxicity. Combined pharmacotherapy and psychotherapy may result in superior therapeutic responses. Psychotherapy is a potential tool deliberately to manipulate environmental factors that influence physiological and physical chemical parameters that determine drug disposition.

Animals↗

Reduction of incorrect antibiotic dosing through a structured educational order form.

Antibiotics are often used inappropriately in hospitals. We created a structured antibiotic order form designed to guide physicians toward correct therapeutic decisions without restricting their clinical options. Educational messages and graphic reminders were incorporated into a new form required to order parenteral antibiotics at a teaching hospital. Pharmacokinetic considerations were emphasized. The forms were supplemented with brief literature reviews and appropriate references. Before introduction of the form, pharmacokinetically incorrect orders for clindamycin, cefazolin sodium, and metronidazole hydrochloride accounted for 90%, 60%, and 75% of patient-days of therapy for these drugs, respectively. Immediately after implementation of the form, nonrecommended dosing schedules dropped to under 6% of patient-days for all three antibiotics. Savings from these drugs alone accounted for over $76,000 annually. We conclude that in a period of increasing constraints on hospital budgets and proliferating restrictions on physicians' clinical choices, educational intervention at the time orders are written can provide a cost-effective and noncoercive means of improving some forms of acute-care clinical decision making.

Anti-Bacterial Agents↗

Effects of adenosine on glucuronidation and uridine diphosphate glucuronic acid (UDPGA) synthesis in isolated rat hepatocytes.

Dibutyryl cyclic adenosine 3':5'-monophosphate (DBcAMP) has been shown to inhibit glucuronidation of p-nitrophenol in a concentration-dependent manner in isolated rat hepatocytes. Adenosine (ADO) also decreased glucuronidation in a similar fashion. The effects of adenosine were examined on the variables controlling glucuronidation in intact cells. The addition of adenosine was without effect on either glucuronyltransferase or beta-glucuronidase. Adenosine decreased uridine diphosphate glucuronic acid (UDPGA) levels by 62% and, subsequently, inhibited glucuronidation by 41% in isolated rat hepatocytes. Since the synthesis of UDPGA requires NAD+ for the dehydrogenation of UDP-glucose, alterations in the redox state could account for the decrease in intracellular UDPGA levels. The effects of ADO (500 microM) on lactate and pyruvate content and redox state were examined in rat hepatocytes. ADO caused a 2.1-fold increase in lactate levels and a 2.65-fold increase in the [lactate]/[pyruvate] ratio. The NAD+/NADP ratio, therefore, was decreased by 63% in the presence of ADO. Carbohydrate reserve also affects UDPGA levels; thus, graded concentrations of glucose (5.5, 25, and 50 mM) were added to cells incubated with ADO. At 5.5 mM glucose, ADO caused a 61% decrease in glucuronide formation, while at concentrations of 25 and 50 mM glucose, the inhibition was diminished by 53 and 47% respectively. ADO appears to have decreased the synthesis of UDPGA by decreasing the NAD+/NADH ratio, thus inhibiting UDP-glucose dehydrogenase. Carbohydrate reserve also appears to be involved in the inhibition of glucuronidation mediated by ADO.

Adenine Nucleotides↗

Effects of age on antidepressant kinetics and memory in Fischer 344 rats.

Experiments were conducted in young (3-4 months) and old (24-25 months) male Fischer 344 rats to assess the effects of amitriptyline, scopolamine, and zimelidine on short term memory using an eight arm radial maze paradigm. Kinetic analyses employing serial blood sampling were also conducted for amitriptyline and zimelidine in an attempt to determine if age-related deficits in performance could be related to changes in pharmacokinetics. In the maze, acquisition of performance was significantly decreased in old rats compared to young. Amitriptyline (5 mg/kg) produced a significant decrement in maze performance on day four of a five day testing period in both young and old rats, while scopolamine (1 mg/kg) produced an initial decrement on day one, followed by a return towards pre-treatment levels in these two age groups. Zimelidine (5 mg/kg) produced no performance decrement in either young or old rats. Kinetic analyses revealed an increased half-life, slower plasma clearance, and a larger volume of distribution of amitriptyline and zimelidine in old rats. Although the kinetic parameters in aged rats exhibited a change in the direction of a decreased ability to metabolize both drugs, this change was not of sufficient magnitude to produce an additive detrimental effect on maze performance.

Aging↗

Changes in phase I and phase II biotransformation with age in male Fischer 344 rat colon: relationship to colon carcinogenesis.

Using male Fischer 344 rats classified as young (2-4 months), middle aged (12-14 months), and old (22-25 months), the activities of several Phase I and Phase II biotransformation pathways in the large intestine were investigated, including benzo[a]pyrene hydroxylase (BPOH), alcohol dehydrogenase (ADH), glutathione S-transferase (GST), glutathione peroxidase (GSH-PX), beta-glucuronidase (BG), and microsomal and nuclear glucuronyltransferase (UDPGT). Levels of oxidized (GSSG) and reduced (GSH) glutathione and uridine 5'-diphosphoglucuronic acid (UDPGA) were also measured. BPOH increased 33% in old rats, while ADH and BG activity remained unchanged with age. Nuclear UDPGT remained unchanged with age, whereas form I of GSH-PX declined slightly in old rats. GST, microsomal UDPGT, and form II of GSH-PX declined by 38, 37 and 44%, respectively, in old rats. The decrease in GST and microsomal UDPGT was also significant in middle aged rats. Levels of colonic GSH, GSSG and UDPGA were found to be unchanged with age. These in vitro data suggest the possibility that if reactive intermediates are generated to the same extent in old rats as in young rats, decreased detoxification mechanisms in the old rat may increase susceptibility of the colon to actions of chemical carcinogens.

Aging↗

Osteosarcoma: relation between extent of marrow infiltration on CT and frequency of lung metastases.

Thirty-seven patients with osteosarcoma were evaluated by CT of both the involved bone and the lungs. The ratio of the extent (E) of the involved marrow segment to the length (L) of involved bone (E/L) was correlated with the presence and subsequent development of pulmonary metastases. The marrow was evaluated by CT for the presence of tumor by measuring mean attenuation coefficients on serial axial scans. Three patient groups were identified: group 1 consisted of seven patients with lung metastases at presentation (mean E/L = 61%), group 2 consisted of 10 patients who developed lung metastases or recurrent tumor either during or after chemotherapy (mean E/L = 39%), and group 3 consisted of 20 patients who completed therapy and remained disease-free (mean E/L = 28%). All patients received chemotherapy in addition to surgical resection except for two patients in group 1. No patient with an E/L ratio greater than 50% remained disease-free for more than 14 months after the initial diagnosis. Fifty percent or greater involvement of the marrow cavity thus carries a particularly poor prognosis, and its absence or presence can be used as a significant prognostic aid in osteosarcoma.

Adolescent↗