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Biomedical subjects
Publications and source records attributed to R Stewart.
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OBJECTIVE: To compare the intraocular pressure (IOP) elevating potential of 1.0% rimexolone and 0.1% fluorometholone alcohol ophthalmic suspensions in patients known to have responded to corticosteroids. DESIGN: In a double-masked, randomized, single-eye, crossover protocol, corticosteroid responsiveness initially was verified in 40 asymptomatic known steroid responders by challenge with either 0.1% dexamethasone sodium phosphate or 1.0% prednisolone acetate for up to 6 weeks. After a 1-month medication washout, subjects randomly received either rimexolone or fluorometholone for 6 weeks. Medications were again discontinued for 1 month, and subjects then received the alternate drug for 6 weeks. RESULTS: There was no significant difference between rimexolone and fluorometholone in the number of subjects demonstrating a 10-mm Hg increase in IOP or in the mean number of weeks required to achieve a 10-mm Hg response. Responses occurred in significantly more subjects receiving dexamethasone sodium phosphate (P = .001) or prednisolone acetate (P < .001) and in a significantly shorter interval than in subjects receiving rimexolone. CONCLUSIONS: Rimexolone has a low IOP-elevating potential, comparable to that of fluorometholone and less than that of dexamethasone sodium phosphate and prednisolone acetate.
Both endogenous lectins and DC electric fields may control aspects of early nerve growth and nerve guidance. To test whether such endogenous cues interact, lectins of varying sugar affinity and valency were studied for effects on electric field induced growth and reorientation of cultured Xenopus neurites. Concanavalin A (Con A), succinylated concanavalin A (S-Con A), and wheat germ agglutinin all completely inhibited field-induced cathodal reorientation. Lentil and pea lectins, which share the same sugar affinity as Con A/S-Con A, were only partially effective in inhibiting reorientation. Because S-Con A does not alter lateral mobility of membrane receptors, the previously accepted notion that Con A inhibited field-induced reorientation by preventing receptors from translocating and becoming redistributed asymmetrically in the membrane may be oversimplified. There are likely to be additional steric interactions that Con A and S-Con A share that inactivate asymmetrically redistributed receptors and prevent reorientation. Additionally, nerves growing in an applied field branch more commonly toward the cathode. Con A and S-Con A alone prevented this development of asymmetric branching. All the lectins tested prevented the normal field-induced increase in nerve growth rate, while all, except peanut agglutinin, prevented the usual faster growth cathodally than anodally. We suggest that lectin interactions with electric field effects in vitro may involve modulation of neuronal nicotinic acetylcholine receptors, neurotrophin receptors, or voltage-dependent calcium channels. Similar interactions between endogenous lectins and endogenous electric fields are to be expected.
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The Dunning rat prostatic carcinoma is a model system where cell motility closely correlates with the metastatic phenotype. We have identified a novel gene, upregulated in the highly motile and metastatic Dunning cancer cell lines, that represents a new member of the thymosin-beta family, thymosin beta 15. Transfection of antisense thymosin beta 15 constructs into rat prostatic carcinoma cells demonstrates that this molecule positively regulates cell motility, a critical component of the metastatic pathway. Thymosin beta 15 levels are elevated in human prostate cancer and correlate positively with the Gleason tumor grade. Thymosin beta 15 may represent a potential new biochemical marker for human prostate cancer progression.
Rickettsiae were isolated by cell culture of buffy coat blood from six patients with spotted fever from southeastern Australia and Flinders Island in Bass Strait. The isolates were genetically compared with two previous Rickettsia australis patient isolates. The genus-specific 17-kDA genes from the isolates were compared after DNA amplification and restriction fragment analysis of the amplified DNA. This comparison revealed that mainland rickettsial isolates from southeastern Australia were identical to two previous isolates of R. australis from northeastern Australia. Rickettsial isolates from Flinders Island were distinct from the mainland isolates. The 16S rRNA gene sequences from the isolates were determined and compared. The Flinders Island rickettsial agent was most closely related (0.3% structural divergence) to Rickettsia rickettsii, Rickettsia conorii, and Rickettsia slovaca. The Flinders Island rickettsial agent was 1.3 and 2.1% structurally divergent from R. australis and Rickettsia akari, respectively. The 16S rRNA gene sequence from the Flinders Island agent shows that this rickettsia is more closely related to the rickettsial spotted fever group than is R. australis. We conclude that there are two populations of spotted fever group rickettsiae in Australia and propose that the genetically distinct causative organism of Flinders Island spotted fever be designated Rickettsia honei. The extent of distribution and animal host reservoirs remain to be elucidated.
This article reviews the common pharmacologic agents used in conjunction with the IABP for treatment of LV failure. The complex interaction between the IABP and pharmacologic agents must be carefully monitored to optimize outcome in this critically ill patient group. It is important that ICU nurses be aware of the treatment goals and their rationale, as well as monitored parameters which detect, trend and predict the direction of hemodynamic change. By using these early indicators of hemodynamics, early information can be given to the physician and intervention can be implemented on a timely basis. Early and appropriate intervention can improve outcome in many patients and may ultimately reduce costs.
Arantius (1571) was the first to describe tortuosity of the splenic artery. The present study investigated the variations in its tortuosity in man, and possible relationships with age, sex, and presence of atheroma. Twenty-nine cadaveric specimens and forty-four celiac angiograms were studied. The straight distance from the origin of the splenic artery, from the celiac trunk, to the point of commencement of the hilar branches was measured, as was the total length of the artery between these two points. The ratio of these two measurements is called the "index of tortuosity." The cadaveric arteries were then opened and graded for the presence of atheroma on a scale of 0 to 3. Marked variation in the index was found in both the cadavers and the angiograms. No definite relationship was found with sex. However, there was a suggestion of increasing tortuosity with age, although in one 10-year-old girl, marked tortuosity was demonstrated on angiography. No significant correlation was shown between increased tortuosity and the extent of atheroma. At present, there is apparently no satisfactory explanation for tortuosity of the splenic artery.
The direction and rate of earliest nerve growth are critical determinants of neuronal architecture. One extrinsic cue that influences these parameters is a small direct current electric field, although the underlying mechanisms are unclear. We have studied the orientation, rate of growth, and branching behavior of embryonic Xenopus spinal neurites exposed to aminoglycoside antibiotics, to raised external cations, to applied direct current electric fields, and to combinations of these treatments. Field-induced cathodal turning and cathodal branching of neurites were blocked by the aminoglycosides, by raised extracellular calcium ([Ca2+]0) and by raised extracellular magnesium ([Mg2+]0). Neomycin together with high external Ca2+, by contrast, induced a reversal in the polarity of turning and branching, with neurites reorienting and branching more frequently anodally. Aminoglycosides decreased neurite growth rates, and for neomycin this was partially reversed by high external Ca2+. Raised [Ca2+]0 alone but not raised [Mg2+]0 altered growth rates in a field-strength dependent manner. Modulation of membrane surface charge may underlie altered galvanotropic orientation and branching. Such an effect is insufficient to explain the changes in growth rates, which may result from additional perturbations to Ca2+ influx and inositol phospholipid metabolism.
In culture, embryonic spinal neurites from Xenopus laevis show striking growth responses to steady dc electric fields, at a time when endogenous electric fields of similar size impinge on the developing nervous system. A high proportion of cultured neurites reorient, with both turning and branching directed cathodally. Neurite growth rates are increased and growth is differential (faster cathodally than anodally). Voltage-dependent calcium channels and calcium release from intracellular stores are shown to control these events. However, the pharmacological sensitivities of these phenomena differ, indicating different control mechanisms.
We have tested the therapeutic potency of peritumorally injected low doses of interleukin-2 (IL-2). Seventy tumours of the bovine ocular squamous-cell carcinoma (BOSCC), 1-3 cm in diameter, were treated with 5000, 20,000 or 200,000 U IL-2 from Eurocetus (Chiron) to find the optimal dose for treatment. Injections were given peritumorally on Monday to Friday on 2 consecutive weeks. The size of the tumours was measured before treatment and 1, 3, 4, 9 and 20 months after treatment. After 9 months complete regression was observed in 89% of the tumours treated with 5000 U IL-2, 80% treated with 20,000 U and 67% treated with 200,000 U. After 20 months, there was complete regression of 35%, 31% and 67% of the tumours respectively. The 9- and 20-month results of the 200,000-U treatment are significantly better than those of the 5000-U and 20,000-U treatments taken together. This protocol may be useful to treat advanced inoperable tumours (e.g. of the nasopharynx or skin) of human patients.
This prospective, randomized, multicenter clinical trial compared the safety and efficacy of the Provisc and Healon viscoelastics. Sixty-one eyes of 61 patients had an extracapsular cataract extraction with implantation of a posterior chamber intraocular lens with the aid of Provisc (n = 32) or Healon (n = 29). Mean changes in preoperative versus postoperative corneal thickness and intraocular pressure and the incidence and magnitude of postoperative corneal edema and iritis were not significantly different between the two groups. Observed complications were considered consequences of the surgery and unrelated to viscoelastic use. No adverse medical events occurred. These results indicate Provisc and Healon are clinically equivalent in terms of safety and efficacy when used as surgical aids.
We describe the first case of prosthetic valve endocarditis due to a Streptomyces sp. The patient presented with fever, cutaneous embolic lesions, and bacteremia 3 months after aortic valve replacement. Treatment required valve replacement and a long course of parenteral imipenem.
OBJECTIVE: To investigate changes in attendance over the course of a population based breast screening programme. DESIGN: Longitudinal; analysis of registered data over nine screening rounds. SETTING: Subjects belong to the screening population of the Nijmegen experimental breast screening programme (1975-1990). SUBJECTS: A cohort of 6898 women who were enrolled in 1975 at the age of 50-69 years and who were invited to nine subsequent screening rounds, irrespective of their attendance at previous rounds. RESULTS: Attendance of women aged 50-53 years at entry was high at the initial screening (88%), decreased in the course of the programme, but remained well over 60% until round 8; 39% completed nine rounds and 24% completed seven to eight rounds. Attendance of women who were older at entry was somewhat lower at the initial screening (87%-82%) and declined more strongly. Regular compliance was also lower. Specific compliance patterns are found that can be relevant for further research. CONCLUSIONS: A substantial proportion of eligible women can be committed to mammography every two years, possibly even after reaching the age of 70, if the age at entry is around 50 and the screening programme is well established in the community. Starting a screening programme in older women seems ineffective.
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The plasma tetracaine concentration versus time profiles for liposome-encapsulated tetracaine (LET) versus nonliposome-encapsulated tetracaine (NLET) were determined after topical application to open wounds in six rabbits (three in LET and three in NLET). H3-tetracaine preparations of LET or NLET were applied randomly to uniform dermal lacerations in anesthetized rabbits. Plasma tetracaine concentrations (ng/mL) of arterial blood samples obtained were measured at predetermined intervals (0.25, 0.5, 1.0, 2.0, and 24 hours) by isotope tracer assay. Results (mean +/- standard deviation) showed the peak plasma tetracaine concentration (Cmax) and the time to Cmax were 40.8 +/- 5.1 ng/mL and 40.1 +/- 7.3 minutes for LET, and 117.8 +/- 9.7 ng/mL and 49.1 +/- 50.2 minutes for NLET. Plasma tetracaine concentrations at all samples times were significantly lower for LET versus NLET. Liposome encapsulation of topically applied tetracaine significantly decreases both the peak and overall plasma tetracaine concentrations compared with the nonencapsulated form. The data suggest that liposome encapsulation of topically applied local anesthetics such as a solution of tetracaine, adrenaline, and cocaine, might reduce the potential systemic toxicity caused by rapid absorption of these compounds.
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