Biomedical subjects
Publications and source records attributed to S R Smith.
Submucosal dissection of the oesophagus is a rare oesophageal disorder. We report a patient who had recurrent episodes of dissection and achalasia. Both recurrence and the association with achalasia are to our knowledge unique.
Twenty-four hours of complete unilateral ureteral obstruction (UUO) produces intense renal vasconstriction in the rat even after release of obstruction. In the ex vivo perfused hydronephrotic rabbit kidney, bradykinin stimulates increased production of the vasoconstrictor autocoid thromboxane. In the present study, we measured basal and bradykinin-stimulated thromboxane and prostaglandin E2 production by UUO and contralateral rat kidneys perfused ex vivo. Furthermore, we evaluated thromboxane synthetase inhibition by imidazole and by two of its substituted derivatives, UK 37248 and UK 38485, in vitro. We compared these in vitro findings with in vivo measurements of renal hemodynamics and excretory function before and after the intrarenal artery administration of thromboxane synthetase inhibitors. Both basal and bradykinin-stimulated thromboxane and prostaglandin E2 production were significantly increased in hydronephrotic kidneys. Imidazole and its substituted congeners were effective inhibitors of bradykinin-stimulated thromboxane B2 production in vitro. However, the substituted imidazoles were more potent, more efficacious, and more selective for thromboxane synthetase inhibition than the parent compound. In vivo, administration of imidazole into the renal artery of the UUO kidney improved function slightly, whereas administration of UK 37248 or UK 38485 doubled renal blood flow and excretory function but did not restore them to normal. We conclude that the hydronephrotic rat kidney produces increased amounts of the vasoconstrictor eicosanoid thromboxane and that thromboxane is an important mediator of vasoconstriction in this model of disease.
A murine monoclonal antibody directed at the platelet glycoprotein IIb/IIIa complex, which blocks platelet aggregation ex vivo, was tested for its antithrombotic effects in an established animal model of acute platelet thrombus formation in partially stenosed arteries. Infusion of 0.7 to 0.8 mg/kg of the F(ab')2 fragment of the antibody completely blocked new thrombus formation despite multiple provocations, making it the most potent antithrombotic agent tested in this model.
A quality assurance program for a clinical pharmacokinetics service that meets current Joint Commission on Accreditation of Hospitals (JCAH) requirements for quality assurance is described. The clinical pharmacokinetics service is provided by pharmacists who have been certified through a staff development program. The clinical pharmacokinetics quality assurance program is part of the department's overall quality assurance program. Information from records maintained by pharmacists who are involved in the pharmacokinetics service is reviewed monthly and compared with 14 criteria that were approved by the pharmacy and therapeutics committee. Results of the monthly audits are summarized in a trend report; these results are communicated to the pharmacists involved, and any necessary corrective actions are taken. The program has led to more appropriate selection of target peak and trough serum drug concentrations, improved documentation of patient data, and better monitoring of each patient's renal function. Physician use of the service has increased as the quality of the service has improved. The quality assurance program has provided mechanisms for monitoring the quality of patient-care services and satisfying current JCAH requirements.
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Beta 2-agonists are known to cause a range of unwanted biochemical and cardiovascular responses. The present study was designed to investigate the effect of chronic exposure to beta 2-stimulation on the magnitude of these responses produced by an acute challenge with a beta 2-agonist. In this single blind placebo controlled study in six healthy male volunteers, we have compared the effects of chronic dosing with either oral terbutaline (5 mg three times daily for two weeks) or placebo on a number of these responses produced by an intravenous infusion of terbutaline (6 micrograms per kilogram over 1 hour). The infusion was given twenty-four hours after the last dose of oral terbutaline or placebo. The rise in pulse rate, systolic blood pressure and plasma glucose and the fall in serum potassium during terbutaline infusion, although still demonstrable, were significantly reduced following treatment with oral terbutaline compared to placebo. This suggests downgrading of beta-receptor function after chronic beta 2-stimulation.
Several pharmacological agents, some of which are known to have effects on the immune system, decrease the incidence of collagen II-induced arthritis when added to the antigen emulsion. Concanavalin A, which has been reported to exert suppressive effects on the immune system in vivo, consistently reduced the immune response to the collagen antigen. These effects were dose and time dependent. The suppressive effects of pokeweed mitogen, tilorone and carrageenan on anti-collagen II responses were somewhat variable. Suppressive activity could be observed with concanavalin A and levamisole when the drugs were injected at a site distant from the collagen emulsion. These studies indicate that local administration of drugs is an effective approach for demonstrating the activity of some agents that may alter the course of collagen II disease through an effect on the immune system.
The dielectric properties of two low-water-content tissues, bone marrow and adipose tissue, were measured from 1 kHz to 1 GHz. From 1 kHz to 13 MHz, the measurements were performed using a parallel-plate capacitor method. From 10 MHz to 1 GHz, a reflection coefficient technique using an open-ended coaxial transmission line was employed. The tissue water contents ranged from 1 to almost 70% by weight. The dielectric properties correlate well with the values predicted by mixture theory. Comparison with previous results from high-water-content tissues suggests that bone marrow and adipose tissues contain less motionally altered water per unit dry volume than do the previously studied tissues with lower lipid fractions. The high degree of structural heterogeneity of these tissues was reflected in the large scatter of the data, a source of uncertainty that should be considered in practical applications of the present data.
Plasma oxprenolol concentrations were measured in six young healthy female volunteers after single oral dosing with a 16/260 oxprenolol Oros system on three separate occasions. Reproducibility was assessed by comparing individual plasma profiles, areas under the curve, peak concentrations and times to peak. Plasma concentration-time profiles were consistent with an extended duration of drug release from the Oros system. Individual and mean profiles on the three occasions were similar, and no significant differences in mean plasma levels, or derived pharmacokinetic parameters, were detected. The mean amount of drug in eight systems recovered from faeces corresponded to 11% of the dose. Individual amounts were related to the total transit time of the system through the body. The 16/260 Oros system functioned reproducibly within the gastrointestinal tract, and in vivo absorption mirrored in vitro drug release.
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The medical records of 412 residents of three southeastern Massachusetts nursing homes were reviewed to examine the frequency and medical management of urinary incontinence and the indications for chronic urinary catheterization. The mean age of the patients was 84.1 years. In this study 9.7% of the patients were managed with a urinary catheter, while an indication for catheterization was recorded in the medical records of only 27.5% of these patients. Half of the noncatheterized nursing home patients were transiently or permanently incontinent of urine, but were not catheterized. Incontinent patients without catheters were more likely to require assistance in toileting (75.5 v 26.1%) or to have bacteriuria (60.1 v 26.1%) than continent patients. Despite the frequency of urinary incontinence, this problem was included in the medical problem list of less than 5% of the incontinent nursing home patients. The authors conclude that urinary incontinence is a frequent medical problem in the nursing home population, but it is rarely recorded and evaluated as a medical problem. Furthermore, indications for urinary catheterization frequently are also not recorded. An explanation for this practice was not determined, but possibilities include a lack of physician knowledge of the evaluation and management of incontinence and a nonaggressive approach to such patients, given their other medical problems.
The principle factor governing the efficacy of a drain is the tissue reaction to the constituent material. This was appreciated during the early development of drainage. Modern materials have been available for more than 20 years but have escaped sound clinical evaluation. In abdominal surgery there is virtually no evidence to support routine intraperitoneal drainage especially with latex rubber unless it is intended to create a fibrous tract as with T-tube drainage of the biliary tree. When drainage is used either static symphonage (Fig. 7), low pressure suction or sump suction with a bacterial air inlet filter should be employed. Silicone rubber (Silastic) tubes are the preferred material. In the parietes closed suction drainage is safe and has achieved a sound reputation for improving healing where serosanguinous oozing is expected. High pressure suction is probably the most effective system. Because of the risk of infection, open drainage systems should, in general, be avoided, especially where a prosthesis is present. Finally, if in doubt, all surgeons should recall the words of Halsteads in 1898 "No drainage at all is better than the ignorant employment of it" rather than the advice of Lawson Tait.
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The extent to which the serum potassium rose in a group of six healthy volunteers during an intra-venous infusion of potassium was identical following pretreatment with placebo, low or high dose propranolol and low or high dose metoprolol. Thus in this acute study, we were unable to demonstrate any influence of either selective or non-selective beta adrenergic blockade upon potassium uptake mechanisms. This is in contrast to the effects of beta blockers on potassium reuptake rates noted after exercise and during cardiac surgery.
The plaque-forming cell (PFC) response to sheep erythrocytes (SRBC) is suppressed in a dose-related manner when concanavalin A (Con A) is administered intravenously to mice prior to or after immunization with antigen. The magnitude of suppression as well as the duration of the Con A effect greatly depends on the concentration of antigen used for immunization. Although profound suppression of the anti-SRBC PFC response is observed in intact mice pretreated with Con A for 4-24 hr, spleen cells from these mice do not exhibit suppressive activity when transferred into normal recipients or when cotransferred with normal spleen cells into irradiated recipients. Moreover, the cells from Con A-treated mice respond as normal spleen cells to SRBC when transferred alone into irradiated hosts. Suppression of the anti-SRBC PFC is only observed when adoptive hosts of cells from Con A-treated mice are also injected with Con A within 48 hr (but not 72 hr) of cell transfer and immunization. This time course of responsiveness to the suppressive effects of Con A is similar to that observed in normal mice and in irradiated recipients of normal spleen cells. The immune response to SRBC is also suppressed in adoptive hosts of normal spleen cells that are pretreated with Con A 4-24 hr prior to irradiation and cell transfer. Although functionally inactive when transferred into adoptive hosts, spleen cells from mice pretreated with Con A for 4-24 hr can suppress a primary antibody response to SRBC in vitro. The suppressive activity, which cannot be detected in the spleens of mice when the interval between pretreatment and assay is longer than 24 hr, is present in a subpopulation that bears the Thy 1.2 and Lyt 2 phenotype. Taken together the results obtained in in vivo and in vitro functional assays suggest that a suppressor cell population is activated following in vivo treatment with Con A, but that the cells rapidly lose their state of activation when removed from a Con A environment. This phenomenon is in all probability responsible for the failure to demonstrate suppressive activity in the spleens of Con A-treated mice using in vivo functional assays.
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Higher AUC and Cmax values were obtained for metoprolol, oxprenolol and propranolol in groups receiving the low-dose oestrogen-ethinyl oestradiol oral contraceptive, but statistical significance was reached only with metoprolol AUC. The oral contraceptive had the opposite effect on acebutolol AUC and Cmax but this was not significant. The oral contraceptive had no detectable effects on the tmax and t 1/2 values of any of the beta-adrenoceptor blockers.