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Biomedical subjects

L Sloan

Publications and source records attributed to L Sloan.

14 recordsLinked to original sources

Trends, rhythms, and aberrations in global climate 65 Ma to present.

Since 65 million years ago (Ma), Earth's climate has undergone a significant and complex evolution, the finer details of which are now coming to light through investigations of deep-sea sediment cores. This evolution includes gradual trends of warming and cooling driven by tectonic processes on time scales of 10(5) to 10(7) years, rhythmic or periodic cycles driven by orbital processes with 10(4)- to 10(6)-year cyclicity, and rare rapid aberrant shifts and extreme climate transients with durations of 10(3) to 10(5) years. Here, recent progress in defining the evolution of global climate over the Cenozoic Era is reviewed. We focus primarily on the periodic and anomalous components of variability over the early portion of this era, as constrained by the latest generation of deep-sea isotope records. We also consider how this improved perspective has led to the recognition of previously unforeseen mechanisms for altering climate.

Animals↗

The impact of alcohol and alcohol expectancies on male perception of female sexual arousal in a date rape analog.

The impact of alcohol and alcohol expectancies on men's perception of female sexual arousal and men's ability to discriminate accurately female sexual intentions in a dating situation was examined. In a 2 (alcohol) x 2 (expectancy) balanced placebo design, men were exposed to an audiotape of a date rape and asked to signal when the man should stop making sexual advances. On 4 occasions during the vignette, participants rated how sexually aroused the woman on the tape was at that moment. Relative to controls, participants who consumed alcohol or expected to consume alcohol took significantly longer to identify the inappropriateness of the man's sexual behavior toward his date. Similarly, alcohol participants also rated the woman's arousal level significantly higher at the first 2 refusals. Implications of the results are discussed.

Adult↗

Social workers' knowledge of and experience with sexual exploitation by psychotherapists.

A survey of licensed social workers in Texas using self-administered questionnaires revealed that, during the previous 12 months, 17 percent had worked with at least one victim of sexual exploitation by a psychotherapist. Social workers licensed as advanced clinical practitioners, licensed social workers with master's degrees, and those working in private practice were most likely to have worked with a victim of such sexual exploitation. Most respondents were not familiar with the provisions of new Texas legislation concerning sexual exploitation by psychotherapists, including definitions and reporting requirements. The majority indicated they would be interested in additional training.

Crime Victims↗

Does inflammation contribute to the eradication of basal cell carcinoma following curettage and electrodesiccation?

BACKGROUND: Curettage and electrodesiccation (C&D) is probably the technique most frequently utilized by dermatologists to treat basal cell carcinomas (BCC). From histologic studies, it appears C&D does not completely mechanically remove all nests of BCC in a substantial number of cases. Nevertheless, the reported 5-year reoccurrence rate following C&D is significantly less than this histologically observed residual tumor frequency immediately following C&D. Among the multiple possibilities that exist to explain why these residual nests do not appear as recurrent tumor more frequently is the theory that inflammation developing after C&D clears residual tumor. OBJECTIVE: To test the hypothesis that inflammation developing after C&D clears residual tumor not mechanically removed by the procedure. METHODS: The frequency of residual BCC detected histologically immediately following C&D was compared with the frequency 1 month after the C&D, an amount of time in which an effect (if any) of inflammation could occur. RESULTS: Twenty-two of 29 primary BCC < 1 cm treated by C&D were tumor free immediately following the procedure (clearance rate, 75.9%). Eleven of 14 primary BCC < 1 cm treated by C&D then allowed to granulate 1 month before excision and histologic analysis were tumor free, for a clearance rate of 78.6%. Examination of larger tumors immediately following C&D revealed size is a significant variable for clearance rates. Eleven primary BCC > 1 cm but < 2 cm were examined histologically immediately following C&D; only three were tumor free for a clearance rate of 27.3%. Only one of five tumors > 2 cm thus treated was tumor free, for a clearance rate of 20%. Nine recurrent BCC of various sizes were treated by C&D and immediately examined histologically. Two were tumor free for a clearance rate of 22.2%. Two recurrent BCC were allowed to heal 1 month following C&D; one of these was tumor free when excised. CONCLUSION: For primary BCC < 1 cm, no evidence was found that inflammation occurring over 1 month following C&D clears residual tumor. It was also noted that C&D fails to completely remove tumor in a large majority of primary BCC > 1 cm, and in recurrent BCC.

Aged↗

Evaluation of enzyme-linked immunoassay for serological diagnosis of cysticercosis.

We evaluated a commercially available enzyme-linked immunoassay (ELISA) from LMD Laboratories, Inc., Carlsbad, Calif., for the detection of antibodies in serum to the cysticercus of Taenia solium. The ELISA was performed on 308 serum samples; 198 from a pool of healthy individuals, 42 from patients who had antibodies against a variety of parasites other than T. solium, and 68 from patients suspected of having cysticercosis. All of these 68 specimens were tested both by the ELISA and by an immunoblot method (enzyme-linked immunoelectrotransfer blot assay [EITB]) developed at the Parasitic Serology Laboratory of the Centers for Disease Control and Prevention. Twenty-seven of the 68 serum samples from patients suspected of having cysticercosis were positive by both EITB and ELISA, while 31 were negative by both assays. ELISA results for three and two samples were considered false positive and false negative, respectively, when compared with the results of EITB. Results for an additional five samples were considered equivocal but were technically positive because their optical density readings were slightly above the cutoff value. Three of the 198 serum samples from the bank of serum samples from healthy individuals were also false positive by ELISA (the EITB result for the samples was negative). Six other serum samples from healthy individuals which had equivocal results and the five serum samples from patients with equivocal results were EITB negative. Serum samples containing antibodies against Echinococcus spp. frequently cross-reacted with the cysticercus ELISA antigen (13 of 16 specimens), but serum samples with antibodies against other parasites did not (2 of 26 specimens); all of these serum samples were EITB negative. The commercially available ELISA that we describe is a simple and rapid test. Considering all 308 specimens, the ELISA had a specificity of 93% (when samples with equivocal results were considered negative) or 89% (when samples with equivocal results were considered positive); the sensitivity was 93%.

Animals↗

Multiple metabolic effects of CGRP in conscious rats: role of glycogen synthase and phosphorylase.

Calcitonin gene-related peptide (CGRP) is a neuropeptide that is released at the neuromuscular junction in response to nerve excitation. To examine the relationship between plasma CGRP concentration and intracellular glucose metabolism in conscious rats, we performed insulin (22 pmol.kg-1.min-1) clamp studies combined with the infusion of 0, 20, 50, 100, 200, and 500 pmol.kg-1.min-1 CGRP (plasma concentrations ranging from 2 x 10(-11) to 5 x 10(-9) M). CGRP antagonized insulin's suppression of hepatic glucose production at plasma concentrations (approximately 10(-10) M) that are only two- to fivefold its basal portal concentration. Insulin-mediated glucose disposal was decreased by 20-32% when CGRP was infused at 50 pmol.kg-1.min-1 (plasma concentration 3 x 10(-10) M) or more. The impairment in insulin-stimulated glycogen synthesis in skeletal muscle accounted for all of the CGRP-induced decrease in glucose disposal, while whole body glycolysis was increased despite the reduction in total glucose uptake. The muscle glucose 6-phosphate concentration progressively increased during the CGRP infusions. CGRP inhibited insulin-stimulated glycogen synthase in skeletal muscle with a 50% effective dose of 1.9 +/- 0.36 x 10(-10) M. This effect on glycogen synthase was due to a reduction in enzyme affinity for UDP-glucose, with no changes in the maximal velocity. In vitro CGRP stimulated both hepatic and skeletal muscle adenylate cyclase in a dose-dependent manner. These data suggest that 1) CGRP is a potent antagonist of insulin at the level of muscle glycogen synthesis and hepatic glucose production; 2) inhibition of glycogen synthase is its major biochemical action in skeletal muscle; and 3) these effects are present at concentrations of the peptide that may be in the physiological range for portal vein and skeletal muscle. These data underscore the potential role of CGRP in the physiological modulation of intracellular glucose metabolism.

Adenylyl Cyclases↗

Hemodialysis: evidence of enhanced molecular clearance and ultrafiltration volume by using pulsatile flow.

We describe several in vitro experiments showing evidence that pulsatile flow hemodialysis enhances ultrafiltration volume and molecular clearance as compared with steady flow hemodialysis. A new pulsatile pump and a conventional roller pump were compared using different hollow fiber dialyzers and a simulated blood solution containing urea, aspartame and vitamin B-12 at different flow rates and configurations. Ultrafiltration volume and concentration of urea, aspartame and B-12 were measured and molecular clearance (K) calculated. Ultrafiltration volume markedly increased with pulsatile flow. After 10 min K for urea with pulsatile flow was higher in all experiments even when ultrafiltration was prevented. Clearance of aspartame and B-12 also increased with pulsatile flow. We propose three mechanisms by which pulsatile flow is more efficient than steady flow hemodialysis: greater fluid energy, avoidance of molecular channeling and avoidance of membrane layering. We hypothesize that using pulsatile flow in hemodialysis can significantly shorten the duration of dialysis sessions for most of the patients, and consequently reduce the duration of the procedure and its cost.

Aspartame↗

An unusual case of variegate porphyria with possible homozygous inheritance.

We report an unusual case of variegate porphyria in a young girl with epilepsy, mental retardation and premature adrenarche. Symptoms of porphyria commenced about the age of 12 years and death occurred about 18 months later. The patient had very low protoporphyrinogen oxidase activity in her cultured fibroblasts. Both parents had half the normal activity of this enzyme in lymphocytes and are heterozygous for the abnormal gene for variegate porphyria. Therefore, it is possible that the patient was a homozygous variant. Anticonvulsant therapy and low hepatic 5 alpha reductase activity were probably other contributing factors to the severity of the condition in this patient.

Animals↗

Cardiovascular properties of metkephamid, a delta opioid receptor agonist, in man.

Opioid receptors exist in at least three forms: mu, delta and kappa. Agonists at mu receptors produce orthostatic hypotension in man by a mechanism involving a reduction in baroreflex sensitivity. We describe here the cardiovascular properties of metkephamid, a relatively selective delta opioid receptor agonist. Blood pressure, heart rate and plasma noradrenaline concentration were measured over a 7 h period in eight normal young male volunteers in the supine position and after 70 degrees 5 min head-up tilt, after receiving metkephamid (50 mg intramuscularly) or placebo. Metkephamid increased heart rate in the supine position with no change in blood pressure or plasma noradrenaline concentration. This was accompanied by symptoms consistent with an anti-muscarinic anticholinergic effect. Head-up tilt resulted in substantial hypotension after metkephamid with an attenuated change in heart rate and no increase in noradrenaline concentration. We conclude that delta as well as mu opioid receptor agonists can produce orthostatic hypotension with attenuation of heart rate response. Metkephamid possesses anticholinergic properties not seen with mu receptor agonists, suggesting a possible role of delta opioid receptors in cholinergic activity.

Adolescent↗

Clinical pharmacological studies with the vasodilator endralazine in patients with renal impairment.

The influence of renal impairment on the pharmacokinetics of endralazine was studied in 12 patients; 4 patients on regular haemodialysis therapy (creatinine clearance less than 5 ml/min) and 8 patients with varying degrees of renal impairment (creatinine clearance 11-52 ml/min). Following an oral dose of 10 mg endralazine the mean terminal elimination half-life (beta t1/2) in the dialysis sub-group was prolonged at 7.1 h (range 3.3 to 14 h), compared to 3.6 h in the other renal patients (and compared to 2.3 h in hypertensive patients with normal renal function). After one week's therapy with 10 mg B.D. endralazine in the 8 patients with moderate renal impairment there was a significant increase in beta t1/2 to 8.6 h but there was no significant change in the area under the drug concentration-time curve and no evidence of drug accumulation. In this study those patients with the poorest renal function had the longest beta t1/2 after acute dosing. There was a significant correlation between creatinine clearance and acute beta t1/2 but there was considerable variability in individual patients and, even with severe degrees of renal impairment, major dose adjustments do not appear necessary.

Acetylation↗

Interaction of bisulfite with unsaturated fatty acids.

Sodium bisulfite reacted with unsaturated fatty acids, significantly increasing their polarity as determined by behavior on silica gel thin-layer chromatography. The ultraviolet absorption spectra of unsaturated fatty acids (due to the presence of double bonds) were abolished as a result of the reaction. Fatty acids containing more than one double bond (arachidonate, linolinate, and linoleate) reacted more rapidly with bisulfite than did oleate. When arachidonate double bonds were titrated with bisulfite there was a much larger spectral decrease with the first equivalent of bisulfite added than with each subsequent addition. Vitamin E, vitamin E nicotinate, and butylated hydroxytoluene significantly inhibited the reaction of bisulfite with unsaturated fatty acids. It is suggested that the reaction of bisulfite with unsaturated fatty acids may be a mechanism of SO2 toxicity.

Antioxidants↗