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Biomedical subjects

S Daniels

Publications and source records attributed to S Daniels.

At least 37 records · Page 2Linked to original sources

Using hospital-based case management to reduce payer denials.

Peninsula Regional Medical Center in Salisbury, Maryland, sought to implement a case management program to reduce a rising number of denied claims for avoidable, nonacute-care inpatient days. Initial efforts focused on consolidating functions rather than monitoring and managing care, and denied claims continued to increase. A revised case management program based on assertive resource management rapidly and substantially reduced claim denials.

Case Management↗

Post-synaptic inhibitory mechanisms of anaesthesia; glycine receptors.

(1) The effects on human homomeric alpha1 glycine receptors of 11 general anaesthetics; four barbiturates, two other intravenous anaesthetics, three volatile anaesthetics and two simple gaseous anaesthetics are described. (2) Pentobarbital and thiopental potentiate the current response to bath applied glycine (50 microM) by 200 and 300%, respectively, at clinically relevant concentrations. (3) Neither methohexital nor phenobarbital had any effect on the current response to bath applied glycine (50 microM). (4) Using maximal doses of applied glycine (1 mM) all the barbiturates acted as non-competitive antagonists. (5) Propofol and etomidate potentiate the current response to bath applied glycine (50 microM) by 200 and 10%, respectively, at clinically relevant concentrations. (6) Etomidate acts as a non-competitive antagonist for doses of glycine above the EC50 (197 microM). Propofol was without effect using maximal doses of applied glycine (1 mM). (7) Halothane, chloroform and ether potentiated the response to bath applied glycine (50 microM) by 200, 100 and 200%, respectively, at clinically relevant doses. (8) None of the volatile anaesthetics had any effect using maximal doses of applied glycine (1 mM). (9) Nitrous oxide and xenon potentiated the response to bath applied glycine (50 microM) by 75 and 50%, respectively, at clinically relevant doses. Nitrous oxide also potentiated the response using maximal doses of applied glycine (1 mM). (10) These results suggest a role for glycinergic neurotransmission in the production of anaesthesia.

Anesthesia↗

Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles.

Adenosine deaminase (ADA) deficiency causes lymphopenia and immunodeficiency due to toxic effects of its substrates. Most patients are infants with severe combined immunodeficiency disease (SCID), but others are diagnosed later in childhood (delayed onset) or as adults (late onset); healthy individuals with "partial" ADA deficiency have been identified. More than 50 ADA mutations are known; most patients are heteroallelic, and most alleles are rare. To analyze the relationship of genotype to phenotype, we quantitated the expression of 29 amino acid sequence-altering alleles in the ADA-deleted Escherichia coli strain SO3834. Expressed ADA activity of wild-type and mutant alleles ranged over five orders of magnitude. The 26 disease-associated alleles expressed 0.001%-0.6% of wild-type activity, versus 5%-28% for 3 alleles from "partials." We related these data to the clinical phenotypes and erythrocyte deoxyadenosine nucleotide (dAXP) levels of 52 patients (49 immunodeficient and 3 with partial deficiency) who had 43 genotypes derived from 42 different mutations, including 28 of the expressed alleles. We reduced this complexity to 13 "genotype categories," ranked according to the potential of their constituent alleles to provide ADA activity. Of 31 SCID patients, 28 fell into 3 genotype categories that could express <=0.05% of wild-type ADA activity. Only 2 of 21 patients with delayed, late-onset, or partial phenotypes had one of these "severe" genotypes. Among 37 patients for whom pretreatment metabolic data were available, we found a strong inverse correlation between red-cell dAXP level and total ADA activity expressed by each patient's alleles in SO3834. Our system provides a quantitative framework and ranking system for relating genotype to phenotype.

Adenine Nucleotides↗

Persistence is not always a virtue: tort reform, civil liability for health care, and the lack of empirical evidence.

The efficacy of reforms in the civil system, including professional liability in the health care arena, depends upon the accuracy with which problems are defined. A growing empirical literature argues that the description of the civil justice system underlying the movement for tort reform in the health care arena is not an accurate one. Regardless, that description continues to be used successfully as the basis for a variety of enacted reforms. The interesting question now posed by some researchers is why that description persists despite its lack of empirical verification. This article summarizes the reformers' description; provides an overview of relevant empirical findings; and then draws on a theoretical literature in political science dealing with agenda-setting in the public policy process to answer that interesting question. The article concludes that the image persists because it is successful in a political, not rational, process in which appeals to emotion overshadow reasoned argument.

Causality↗

Outcome study of the psychological changes after silicone breast implant removal.

INTRODUCTION: The purpose of this longitudinal study is to determine if there are changes in psychological well-being after breast implant removal. METHODS: Thirty-seven women underwent breast implant removal and completed a preoperative baseline, early postoperative (4 to 9 months), and late postoperative (> 10 months) Brief Symptom Inventory, a measure of psychological distress. RESULTS: After breast implant removal the mean Global Severity Scores on the Brief Symptom Inventory of women undergoing implant removal increased over the three time periods, indicating increasing psychological distress. When the group was divided into those who had breast reconstruction after implant removal (implant replacement with saline-filled implants or TRAM flaps) and those who did not have reconstruction, both groups had increasing psychological distress, but the women who had reconstruction had slightly higher scores. Women with a history of psychiatric treatment showed the greatest increase in psychological symptoms. CONCLUSION: Breast implant removal did not have psychological benefits in this group of women. Breast reconstruction after removal did not appear to be psychologically beneficial to this cohort.

Adult↗

Glycine activation of human homomeric alpha 1 glycine receptors is sensitive to pressure in the range of the high pressure nervous syndrome.

The effect of hyperbaric pressure on the inhibitory glycine receptor has been investigated in voltage-clamped Xenopus oocytes microinjected with cRNA encoding the human alpha-1 glycine receptor subunit. Heterologous expression of the human alpha-1 subunit generated functional glycine-gated channels with properties typical of native receptors. Glycine elicited a concentration-dependent inward current which reversed polarity at -25 mV and was antagonised by nanomolar concentrations of strychnine. Concentration-response curves established for the homomeric alpha-1 glycine receptor at 5, 10 and 15 MPa were progressively shifted to the right with respect to the concentration response curve established at atmospheric pressure (0.1 MPa). Pressure had no effect on the maximal response. The EC(50) values at 0.1, 5, 10 and 15 MPa were 190 mu M, 222 mu M, 338 mu M and 482 mu M, respectively. The results demonstrate that a receptor comprised solely of the human alpha-subunit is sensitive to pressure in the range that affects divers and at which the native rat spinal cord receptor is affected. This finding is discussed in the context of the postulated binding sites for glycine and the implications for the design of drugs to protect divers from the effects of pressure.

Animals↗

A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis.

Distal ulcerative colitis can be treated with oral or rectal mesalazine, or both. A foam enema preparation has been developed and its efficacy investigated. The aim of this study was to evaluate the efficacy and safety of mesalazine foam enemas compared with prednisolone foam enemas in the treatment of patients with acute distal ulcerative colitis. Patients aged over 18 years presenting with a relapse of distal ulcerative colitis were randomly allocated treatment with mesalazine foam enema (n = 149 evaluable patients) and prednisolone foam enema (n = 146 evaluable patients) for four weeks. A randomised multicentre investigator blind parallel group trial was conducted. It was found that after four weeks of treatment, clinical remission was achieved by 52% of mesalazine treated patients and 31% of patients treated with prednisolone (p < 0.001). There was a trend in favour of more patients in the mesalazine group achieving sigmoidoscopic remission (40% v 31%, p = 0.10). Histological remission was achieved by 27% and 21% of patients receiving mesalazine and prednisolone respectively. Symptoms improved in both treatment groups. Significantly more mesalazine patients had no blood in their stools after four weeks of treatment (67% v 40%, p < 0.001). Prednisolone treated patients had significantly fewer days with liquid stools than mesalazine patients, with a median of 0 and 1 days respectively by week 4 (p = 0.001). In this study mesalazine foam enema was superior to prednisolone foam enema with regards to clinical remission, this was supported by favourable trends in sigmoidoscopic and histological remission rates. Both treatments were well tolerated.

Acute Disease↗

Damage to red blood cells induced by acoustic cavitation.

This experimental study has revealed damage to red blood cells that is quantitatively related to the acoustic pressure during irradiation with 0.75-MHz continuous-wave ultrasound, using a range of intensities comparable to those employed by ultrasonic physiotherapy equipment (0.25 to 7 W cm-2 spatial average temporal average). Damage to the red blood cells was investigated by measuring the extent of haemolysis using a UV/VIS spectrophotometer. There was a clear correlation between the amount of haemoglobin released and the intensity of harmonic emissions recorded from the sample during irradiation. The observed degree of haemolysis could not be produced by temperature rises in the absence of the sound field. This suggests that the damage was a direct result of acoustic cavitation.

Acoustics↗

Efficient reactivation of Xenopus erythrocyte nuclei in Xenopus egg extracts.

Rapid genome replication is one of the hallmarks of the frog embryonic cell cycle. We report here that complete reactivation of quiescent somatic cell nuclei in Xenopus egg extracts depends on prior restructuring of the nuclear substrate and prior preparation of cytoplasmic extract with the highest capacity to initiate and sustain DNA synthesis. Nuclei from mature erythrocytes swell, replicate their DNA efficiently, and enter mitosis in frozen/thawed extracts prepared from activated Xenopus eggs, provided the nuclei are first treated with trypsin, heparin, and an extract prepared from unactivated, meiotically arrested, eggs. Optimal replicating extracts are prepared from large batches of unfertilized eggs that are synchronously activated into the cell cycle for 28 minutes (at 20 degrees C). Because the Xenopus cell cycle progresses so rapidly, extracts prepared just a few minutes before or after this time have substantially lower DNA synthetic capacities. At the optimal time and temperature, eggs have just reached the G1/S boundary of the first cell cycle. This fact was revealed by injecting and replicating an SV40 plasmid in intact unfertilized eggs as described previously. We estimate that under optimal conditions approximately 6.14 x 10(9) base pairs of DNA/per nucleus are synthesized in 30-40 minutes, a rate that rivals that observed in the zygotic nucleus. The findings reported here are one step in our long term effort to develop a new in vitro/in vivo approach to nuclear transplantation. Nuclear transplantation in amphibian embryos has been used to establish that the genomes of many types of differentiated somatic cells are pluripotent. But very few such nuclei have ever developed into advanced tadpoles or adult frogs, probably because somatic nuclei injected directly into activated eggs fail to reactivate quickly enough to avoid being damaged during first mitosis. We have already shown that unfertilized eggs can be injected prior to activation of the first cell cycle. Future experiments will reveal whether in vitro reactivated somatic cell nuclei transplanted into such eggs reliably reach advanced stages of development.

Animals↗

Vaccine storage and handling. Knowledge and practice in primary care physicians' offices.

OBJECTIVE: To assess the knowledge and practice of vaccine storage and handling in primary care physicians' offices. DESIGN: A cross-sectional study was conducted from August to December 1992. Staff responsible for vaccine storage were interviewed about their knowledge and practices of vaccine handling and storage. Refrigerators were inspected to document refrigerator temperature and vaccine storage conditions. SETTING: General and pediatric practices in 12 regions of Ontario. PARTICIPANTS: Practices outside metropolitan Toronto were selected by choosing every 10th physician who ordered vaccine from the local health department in 1992. Practices chosen in metropolitan Toronto were a random selection of physicians affiliated with a Toronto teaching hospital. Eighteen pediatric and 138 general practices were approached to participate; 12 pediatric and 123 general practices participated in the study. The overall response rate was 86.5%. MAIN OUTCOME MEASURES: Survey responses and temperature and storage conditions of refrigerators upon inspection. RESULTS: Fewer than seven (6%) practices answered all questions related to vaccine storage and handling correctly, and only 11 (10%) refrigerators had thermometers. One-third of refrigerators had temperatures outside the recommended range of 2 degrees C to 8 degrees C. Older refrigerators were more likely to have inappropriate temperatures than newer ones. CONCLUSIONS: Knowledge and practice of vaccine storage and handling are often inadequate in primary care physicians' offices.

Clinical Competence↗

Predicting medical student success in a clinical clerkship by rating students' nonverbal behavior.

OBJECTIVE: To evaluate the relative contribution of affective and cognitive skills to ratings of students' clinical performance by their supervisors. METHODS: Each students' nonverbal behavior was analyzed by examining 33 nonverbal behavioral characteristics in videotape of each of 36 students interviewing a parent or patient three times during a 4-week pediatric clerkship. These ratings were then compared with the student's formal academic evaluation. RESULTS: The 33 nonverbal behavioral characteristics rated for each student were reduced to five composite variables. Three of these correlated significantly with the final grade, providing an affective profile of the highly rated student. Regression analysis of the five composite variables revealed that affective skills accounted for at least 46% of the variance in the students' final grades (multiple R = .68, P = .0015). CONCLUSIONS: Ratings of students' affective characteristics were highly related to clinical evaluations in this pediatric setting. Students who were evaluated highly had a specific affective profile that could be described by analysis of their nonverbal behaviors.

Adult↗

Comparison of potencies of 5-HT3 receptor antagonists at inhibiting aversive behavior to illumination and the von Bezold-Jarisch reflex in the mouse.

The inhibitory effects of ondansetron and R and S zacopride on aversive behavior to light and the von Bezold-Jarisch reflex have been compared in mouse. The potencies (ID50, microgram/kg i.v.) of compounds at inhibiting the von Bezold-Jarisch reflex, elicited by 2-methyl-5-HT (mouse 100 micrograms/kg, i.v.; rat 10-80 micrograms/kg i.v.) were: S zacopride (0.02), granisetron (0.17), R zacopride (0.30) ondansetron (3.16). A similar rank order of ID50 values was observed in rat, i.e. S zacopride (0.02), granisetron (0.36), R zacopride (0.25) and ondansetron (2.65). These data suggest that the activity of compounds at 5-HT3 receptors mediating this effect was similar in both mouse and rat. In mouse behavioral studies, ondansetron and R and S zacopride potently inhibited aversive behavior to light (0.0003-30 micrograms/kg, p.o.), when the amount of time spent in the dark and locomotor activity were measured. Thus, at 0.3 ng/kg, the mean percentage time spent in the dark significantly decreased from 84 to 72, for both R and S zacopride, respectively. The maximal effects of these compounds were modest in comparison to the 'anxiolytic' effects of diazepam (0.3-1.4 mg/kg, i.p.; at 0.3 mg/kg the mean percentage time spent in the dark significantly decreased from 84 to 36) or chlordiazepoxide (3-40 mg/kg, i.p.; at 3 mg/kg, the mean percentage time spent in the dark significantly decreased from 85 to 40). The doses of the 5-HT3 antagonists were approx 1000-fold lower than those effective inhibitory doses determined in the von Bezold-Jarisch reflex studies, in either mouse or rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis.

Two hundred and seventy-eight adult chemonaive patients, receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eight-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone.

Adult↗

Local increase in hyaluronic acid and interleukin-2 in the capsules surrounding silicone breast implants.

Connective tissue disease-like illness has been associated with silicone breast implants. However, no data are currently available on the immunopathology of the capsule surrounding the breast implants. Sera from women with breast implants were collected and assayed for interleukin-6 (IL-6), IL-2, and hyaluronic acid. Capsular biopsies were stained with a probe for HYA or with monoclonal antibodies specific for human macrophages (CD68), T cells (CD4), IL-6, and IL-2. Control specimens consisted of breast biopsies from women undergoing reduction mammoplasty. Our results revealed an increased local amount of hyaluronic acid in the capsule of patients with breast implants compared with control breast tissue. The HYA was localized extracellularly in areas containing fibrosis and cellular infiltrates. The infiltrating cells were determined to be primarily macrophages and T cells. No IL-6 was localized in any of the tissue sections. In contrast, large amounts of IL-2 were found in regions of infiltrating lymphocytes. No significant increase in IL-6, IL-2, or hyaluronic acid was found in the sera. The role of hyaluronic acid and cytokines in the inflammatory response in the capsules of silicone breast implants is discussed.

Breast↗

Are oxygen radicals implicated in the calcium paradox of the rat heart?

No reduction in creatine kinase (CK) release during standard Ca2+ paradox in the Langendorff-perfused rat heart was afforded by anoxic perfusion, nor by addition of the radical scavengers superoxide dismutase (150,000 U/L), catalase (150,000 U/L), mannitol (15 or 50 mM), dimethylthiourea (DMTU, 10 mM), the antioxidant vitamin E (0.25 or 0.75 mM), or the iron chelator desferrioxamine (0.8 mM). Even under mild Ca(2+)-paradox conditions, achieved by (a) reducing the duration of the Ca(2+)-free period, (b) increasing [Ca2+]0 during the "Ca(2+)-free" period, or (c) reperfusing with 0.1 mM Ca2+, no protection was achieved by mannitol, DMTU, or desferrioxamine. Perfusion with N2 did not cause a reduction in CK release caused by caffeine or dinitrophenol or Ca2+ paradox. We conclude that no evidence supports the hypothesis that oxygen radicals are implicated in release of CK in Ca2+ paradox.

Animals↗

The use of lymphoscintigraphy in melanoma of the head and neck.

Lymphoscintigraphy has been shown to be of assistance in defining the lymphatic drainage pattern of melanoma. In this study, lymphoscintigraphy was performed on 25 patients with primary melanoma (stages I and II at diagnosis) of the head and neck to determine whether the lymphatic drainage seen on lymphoscintigram was the same as the surgeon's expected lymphatic drainage. The lymphoscintigrams were discordant in 21 of the patients (84 percent) with drainage to a lymphatic basin not predicted clinically. Based on the discordant lymphoscintigram, a change in surgical therapy occurred in 13 of 21 patients (62 percent). Of the 25 patients, 18 underwent prophylactic node dissections and 7 did not. Of the nodal basins removed, 27 of 38 nodal bases (71 percent) were seen on lymphoscintigraphy. Melanoma metastatic to lymph nodes was removed from nodal basins identified by the lymphoscintigram, but not predicted clinically, in two patients (8 percent). Historical anatomical patterns of lymph drainage and the clinical impression of experienced surgeons cannot reliably predict the pattern of lymphatic drainage in patients with melanoma of the head and neck.

Adolescent↗