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Biomedical subjects

S Feldman

Publications and source records attributed to S Feldman.

At least 163 records · Page 9Linked to original sources

Iontophoresis of cortisol inhibits responses of identified paraventricular nucleus neurones to sciatic nerve stimulation.

Responses of paraventricular nucleus (PVN) neurones were examined following stimulation of the sciatic nerve, and concomitant with iontophoretic application of cortisol. Sciatic nerve stimulation excited the majority of cells (22/24, 92%) and iontophoretic application of cortisol reduced the spontaneous activity of 16 of the cells tested (67%). Cortisol prevented neuronal responses to sciatic nerve stimulation in 11 cases (50%) but some of the cells inhibited by the steroid still responded to the stimulation, whilst some cells unaffected by cortisol alone were found not to respond during exposure to the stimulus. These results indicate an inhibitory role for glucocorticoids in the regulation of PVN neuronal activity and responses to afferent neural stimuli.

Action Potentials↗

Simultaneous determination of physostigmine and tetrahydroaminoacridine in a transdermal permeation study by high-performance liquid chromatography.

A selective and stability-indicating high-performance liquid chromatographic assay with diazepam as the internal standard was developed for simultaneously analyzing physostigmine and tetrahydroaminoacridine in skin samples, permeation diffusates and dosage form. Baseline resolution was achieved with an octadecyl column for physostigmine, its two degradation products and tetrahydroaminoacridine. Peak homogeneity of physostigmine and tetrahydroaminoacridine was confirmed. The calibration curves for both drugs in skin samples were established at 1-50 micrograms per 200 mg skin. Those for diffusate samples were at 10-50 ng per 50 microliters for physostigmine and 30-150 ng per 50 microliters for tetrahydroaminoacridine. The assay was reproducible with within-day and between-day variations of 5-6 and 4-10%, respectively. Application of the assay for in vitro transdermal permeation study was demonstrated.

Aged↗

Effect of concurrent sucralfate administration on the absorption of erythromycin.

To determine the influence of sucralfate on the absorption of erythromycin, prior to evaluating its efficacy in decreasing erythromycin-associated gastrointestinal (GI) intolerance, we assessed pharmacokinetic parameters in six healthy adult volunteers. Erythromycin ethylsuccinate administered alone or with sucralfate as a single dose was compared. Sucralfate did not significantly alter the elimination rate constant, half-life, or area under the curve for erythromycin ethylsuccinate. It is therefore unlikely that efficacy of erythromycin ethylsuccinate will be altered when sucralfate is coadministered.

Adult↗

The preoptic area and bed nucleus of the stria terminalis are involved in the effects of the amygdala on adrenocortical secretion.

In view of the role of the amygdala in the modulation of adrenocortical secretion we have studied the neural pathways which mediate this response. Changes in plasma corticosterone following medial amygdala stimulation, under pentobarbital anaesthesia, were studied in rats which chronically implanted electrodes in intact and lesioned animals. The rise in plasma corticosterone following amygdala stimulation was inhibited by bilateral lesions of the stria terminals, medial preoptic area, and bed nucleus of the stria terminalis, and to a greater extent by a combined lesion of the latter two structures. The combined lesion also completely blocked the adrenocortical response to olfactory stimulation. These various lesions did not affect, however, the rise in plasma corticosterone following ether stress. These data thus demonstrate that the stria terminalis, preoptic area and bed nucleus of the stria terminalis are involved in the transmission of neural impulses to the hypothalamus which activate adrenocortical secretion.

Adrenal Cortex↗

Adrenal responses and neurotransmitters in posterior hypothalamic deafferentation.

The effects of a small posterior hypothalamic deafferentation (PHD) on adrenocortical responses to peripheral neural stimuli were investigated in rats. PHD inhibited the rise in plasma corticosterone (CS) following photic and acoustic stimulation, but did not affect the adrenocortical response following sciatic nerve stimulation. PHD did not change the content of norepinephrine in the paraventricular nucleus of the hypothalamus, however, it reduced the serotonin content by about 30%. The possible role of serotonin or of another tonic caudal input into the hypothalamus for the activation of the pituitary-adrenocortical axis, following certain neural stimuli, is discussed.

Acoustic Stimulation↗

Disposition of bismuth in the rat. II. Pharmacokinetics and biliary excretion.

The pharmacokinetics and biliary excretion profile of intravenously administered bismuth ions were investigated in male Sprague Dawley rats. The data indicated that in the dose range studied, the percentage of dose excreted in urine ranged from 58 to 63%. The mean residence time for bismuth ions was 3.93, 4.07, and 5.45 hr for the 0.5, 0.75, and 1.0 mg/kg dose, respectively, while the volume of distribution at steady state was 0.75, 1.24, and 1.38 L/kg for the three doses. Blood clearance values ranged from 0.2 to 0.32 L/hr/kg. Blood bismuth ion concentrations toward the latter part of the sampling schedule indicated significant variability. The bile-to-blood concentration ratio of intravenously administered bismuth exceeded 1.0 for the three doses studied, suggesting that transport of bismuth from blood to bile may be carrier mediated.

Animals↗

Disposition of bismuth in the rat. I. Red blood cell and plasma protein binding.

The plasma protein and red blood cell binding profile of bismuth was investigated as a function of bismuth concentration. The binding of bismuth to human serum albumin, bovine serum albumin, and human plasma was also evaluated by ultrafiltration and the data analyzed by nonlinear regression techniques. The binding of bismuth to plasma proteins was nonlinear and decreased as a function of incubation concentration and appeared to be limited by the number of ionized l-cysteine residues available for binding. In the concentration range studied, bismuth was associated primarily with the red blood cell fraction of whole blood obtained from male Sprague Dawley rats. The data indicated that binding to proteins was of moderate affinity, and in whole blood it was present primarily in the red blood cell compartment.

Animals↗

Risk of Haemophilus influenzae type b disease in children with cancer and response of immunocompromised leukemic children to a conjugate vaccine.

From 1969 to 1988, 8 cases of systemic Haemophilus influenzae type b (Hib) disease occurred among 5288 patients with cancer. For the first 4 years of life, systemic Hib disease was significantly greater in leukemic children than in the general population (606/100,000 vs. 90/100,000, respectively). Fifty children aged 2-6 years with acute leukemia were vaccinated with a Hib conjugate vaccine, ProHibit. The overall response rate was 50%; however, 75% of children receiving leukemic therapy for less than 12 months responded versus 18% of those treated longer. After vaccination, the geometric mean antibody concentration was 7.2 micrograms/ml, appreciably lower than for normal children of similar ages. After 12 months, the geometric mean antibody concentration had declined to 0.35 micrograms/ml, and 75% of subjects had antibody levels greater than or equal to 0.15 micrograms/ml. A booster dose for unsuccessfully vaccinated subjects was of minimal benefit. Children with acute leukemia in remission who were treated according to the leukemia therapy protocol of St. Jude Children's Research Hospital had a good likelihood of responding to the conjugate Hib vaccine if administered within a year of initiation of chemotherapy.

Adolescent↗

A triceps musculocutaneous flap for chest-wall defects.

A posterior upper arm flap based on the profunda brachii vessels has been described to cover soft-tissue defects in the upper anterolateral chest. In our series, the posterior upper arm skin is elevated with the long head of the triceps muscle to cover seven chest-wall defects resulting from indolent postradiation open wounds following partial TRAM flap failure (n = 2), soft-tissue deficiencies following partial TRAM flap loss (n = 3), and primarily as an ancillary flap in TRAM flap breast reconstruction (n = 2). This flap also may be used to supply well-vascularized tissue in the regions of the shoulder, axilla, and posterolateral back. A prerequisite for this operation is redundant tissue of the upper arm often present in middle-aged women and in patients with lymphedema following mastectomy. In our series of seven patients, all donor sites were closed primarily, and there was no subjective functional deficit following transfer of the long head of the triceps muscle.

Arm↗

Safety and pharmacokinetics of rimantadine small-particle aerosol.

The safety and pharmacokinetics of rimantadine administered by small-particle aerosol were assessed in healthy adults and adults with acute influenza virus infection. Aerosolized rimantadine delivered at a concentration of 40 micrograms/liter of air was associated with nasal burning and irritation in normal volunteers. A concentration of 20 micrograms/liter of air was well tolerated for up to 12 h by normal volunteers and was not associated with any changes in pulmonary function, as measured by routine spirometry, plethysmography, or diffusion capacity of carbon monoxide. Mean peak levels of drug in serum were approximately 10-fold lower after 12 h of aerosol administration than they were after oral administration of 200 mg (29.7 versus 255 ng/ml, respectively), while mean nasal wash levels were approximately 100-fold higher (6,650 versus 66.6 ng/ml, respectively). Elimination half-lives were similar after both aerosol and oral administration (24.1 and 25.2 h, respectively), and rimantadine urinary excretion was less than 1% per 24 h in both groups. Twenty micrograms of aerosolized rimantadine per liter of air given 12 h daily for 3 days to nine adults with acute influenza virus infection was well tolerated. Levels in plasma after 12 h of aerosol inhalation were similar to those in normal volunteers, but were higher at the end of the third treatment than they were at the end of the first treatment (88.3 versus 47.9 ng/ml, respectively). Thus, rimantadine delivered via small-particle aerosol at a dose of 20 micrograms/liter of air was well tolerated in normal volunteers and in those with acute influenza and was associated with high local concentrations.

Adult↗

Transvenous defibrillation in humans via the coronary sinus.

A consistently effective transvenous defibrillation system for use in automatic defibrillators could significantly alter the approach to patients at risk of sudden death. Transvenous defibrillation systems that use a right ventricular (RV) electrode only or an RV electrode in combination with a chest patch are relatively inefficient at applying current to the posterolateral left ventricle. An RV electrode combined with a coronary sinus (CS) electrode, however, may improve current distribution to the posterolateral left ventricle. The purpose of this investigation, therefore, was to evaluate the effectiveness and safety of a specially designed transvenous lead system with a CS electrode capable of current delivery to this relatively inaccessible region of the heart. In 20 survivors of cardiac arrest, we determined defibrillation efficacy immediately before defibrillator surgery for monophasic pulses delivered between an RV catheter electrode and a CS catheter electrode system and compared these findings with an RV catheter electrode-thoracic patch defibrillation system. Subsequently, we referenced the efficacy of both transvenous systems to an epicardial patch electrode system at the time of defibrillator implantation. The mean delivered-energy defibrillation threshold for the CS-RV electrode system was 17.5 +/- 7.9 J, which was substantially lower than the RV electrode-thoracic patch system (25.6 +/- 11.4 J, p = 0.0016 [46% more]). Defibrillation threshold voltage was 529 +/- 123 V for the CS-RV electrode system and 647 +/- 164 V (22% more) for the RV electrode-thoracic patch system (p = 0.0013).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Vessels↗

Twenty-four hour lung function in adult patients with asthma. Chronoptimized theophylline therapy once-daily dosing in the evening versus conventional twice-daily dosing.

Many patients with asthma experience a worsening of symptoms at night and in the early morning, resulting in sleep disruption and possibly altered daily performance. A bronchodilator agent that exerts its maximal effect overnight to control nocturnal symptoms, without a worsening of the disease during the daytime, should improve the treatment of asthma. This investigation examined the efficacy and kinetics of a new chronotherapeutically optimized, sustained-release theophylline formulation administered once daily (OD) in the evening at 8:00 P.M. in comparison with a conventional sustained-release theophylline administered twice daily (TD) at 8:00 A.M. and at 8:00 P.M. in the same dose. After a theophylline clearance study to substantiate normal or slow metabolism of the drug, a dose-titration period, and a 24-h baseline spirometric study of patients not receiving any medication, participants were randomized to 7-day treatment phases with either OD or TD. Each outpatient segment of 6 days of OD and TD was followed by a 24-h inpatient study on Day 7 when serum drug level and spirometric (PEF, FEV1, and FEF25-75) parameters were obtained every 2 h. The conventional TD treatment was associated with a constant serum theophylline level over the 24 h. In contrast, the OD treatment was associated with larger peak-to-trough drug level fluctuation, with higher levels produced overnight and lower ones in the evening at the end of the dosing interval. Compared with the baseline references, both OD and TD significantly improved airflow over the entire 24 h and to a comparable extent. However, between 2:00 and 6:00 A.M., PEF and FEV1 were significantly greater with OD than with TD. The improvement in PEF and FEV1 at this time, because of OD, was correlated with the serum theophylline level. This was not the case for TD. The improvement in airflow over baseline values between 2:00 and 6:00 P.M. was not correlated with theophylline level with either treatment regime. Overall, the chronotherapeutically conceptualized OD treatment administered in the evening resulted in better airflow levels overnight than did the TD regime without loss of airflow in the afternoon.

Adult↗

Penicillin dosage.

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Actinomycosis↗

Combined penetrating keratoplasty and vitreoretinal surgery with the Eckardt temporary keratoprosthesis.

The Eckardt style temporary keratoprosthesis was used in six cases of five eyes undergoing simultaneous penetrating keratoplasty and pars plana vitrectomy. This device provided excellent visualization of posterior and peripheral intraocular structures and maintained a closed system during surgery. Corneal grafts remained clear in 80% of the cases, and macular attachment was achieved with either silicone oil or perfluoropropane gas in 50% of cases followed for at least 6 months. Visual function remained the same or improved in three eyes. Suggested refinements to the placement of this device include enlarging the trephination to 6.75 mm and the use of 8-0 nylon sutures to prevent cheesewiring of the soft silicone rim. A plano contact lens required during surgery to visualize the retina did not minify the image. Since the optical cylinder of the Eckardt temporary keratoprosthesis is shorter than that of a Landers-Foulks keratoprosthesis of similar diameter, it provides greater peripheral visualization. It is, however, less durable.

Adult↗

Adrenocortical response following acute neurogenic stimuli is mediated by CRF-41.

The present study examined whether neurogenic stimuli activate the pituitary-adrenal axis via CRF-41. Adult male rats were exposed to photic, acoustic or sciatic nerve stimulation. At 4, 15, and 30 min following the onset of stress, animals were sacrificed, trunk blood collected and the median eminence removed. At 4 min following the stress onset, there was a significant decrease in CRF-41 content of the median eminence, which persisted for 30 min. Concomitant with the decrease in CRF-41 content, serum adrenocorticotropic hormone (ACTH) and corticosterone levels increased. Thus, this study demonstrates that CRF-41 released from the median eminence plays a dynamic role in mediating the ACTH and corticosterone response to neurogenic stimuli.

Adrenal Cortex↗