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Biomedical subjects

S Michael

Publications and source records attributed to S Michael.

At least 19 recordsLinked to original sources

Evidence for different ABC-transporters in Caco-2 cells modulating drug uptake.

PURPOSE: Secretory systems contribute to drug absorption in the gastrointestinal tract. The purpose of this study was the identification of members of the ATP binding cassette superfamily of secretory transport proteins that may potentially modulate drug absorption in Caco-2 cells, which are an important cellular model predicting enteral absorption of drugs. METHODS: Kinetic studies as well as PCR- and Western blot studies with confluent epithelial layers of human Caco-2 cells. RESULTS: The study demonstrates functional expression of multidrug resistance related protein (MRP) and P-glycoprotein (P-gp) in Caco-2 cells: 1) Efflux studies with the MRP specific substrate glutathion-methylfluorescein (GS-MF) showed functional activity of MRP in Caco-2 cells preloaded with the metabolic precursor of GS-MF, chloromethylfluoresceine-diacetate, CMFDA. Excretion of GS-MF was decreased in presence of the MRP-blocker M K-571.2) Transport experiments with cyclosporin A demonstrated the functional activity of P-gp. Cellular accumulation was increased in presence of the P-gp blocking agent SDZ-PSC 833. 3) The expression of the 190 kDa protein MRP and the 170 kDa protein P-gp in Caco-2 cells was shown by Western blot analysis with specific monoclonal antibodies. 4) The expression of MRP-mRNA in Caco-2 cells was detected by RT-PCR and compared with the MRP over-expressing cell line H69AR. MRP primers recognize specifically human MRP1 (GenBank accession number L05628), but not all other published sequences of MRP (MRP2-MRP6). P-gp expression on mRNA-level was also confirmed by RT-PCR. CONCLUSIONS: The data demonstrate that besides P-gp, multidrug resistance related protein (MRP) is functionally expressed in Caco-2 cells and contributes to the active excretion of substrates in this cell line.

ATP Binding Cassette Transporter, Subfamily B

A study of the relationship between family history of breast cancer and knowledge of breast cancer genetic testing prerequisites.

Awareness of hereditary breast cancer genetic testing, of breast cancer risk factors, and of increased level of risk based on family history are necessary before women can seek out genetic services. The aim of this paper is to describe the relationships between family history of breast cancer and awareness of genetic testing, knowledge of breast cancer risk factors, and perceived lifetime risk of breast cancer. An anonymous survey was administered by mail to a random sample of 600 women, 200 from each of three breast cancer family history groups (none, intermediate, and strong), drawn from a population-based registry of 240,000 women enrolled in a mammography screening program in the Denver Metropolitan area in Colorado. Awareness of genetic testing for breast cancer risk assessment was found to be significantly associated with family history of breast cancer, increasing from 35% in the lowest family history risk group to 67% in the group with the strongest familial risk (p = 0.002). In all family history groups, nearly 70% of respondents viewed high-fat diet and smoking as being important in relation to breast cancer risk, but alcohol was seen as being only somewhat important or not important by almost half of all respondents. Having a mother or sister with breast cancer was reported as being extremely or very important by nearly all respondents, regardless of family history. As expected, perceived lifetime risk for developing breast cancer was associated with family history (p = 0.001), but the perception of the lifetime risk for breast cancer was much higher among all of the family history groups than their true risk. In conclusion, educational interventions are needed to heighten women's awareness of genetic testing, to clarify women's knowledge of breast cancer risk factors, especially alcohol, and to reassure many women that their actual breast cancer risk is lower than they might perceive.

Breast Neoplasms

Suicidal ideation in Sudanese women.

A literature review indicated that suicidal behavior in Sudan was very infrequent. However, an assessment of suicidal ideation in two Sudanese groups of women demonstrated high levels, particularly in women in a displaced-persons area. In addition, the recent establishment of a Befrienders International volunteer service allowed anecdotal evidence of substantial suicidal behavior to be collated. These findings highlight the need for further professional and volunteer assistance with continuing evaluation and research concerning programs for this vulnerable population.

Adult

Medical care for haemophilia.

BACKGROUND/OBJECTIVES: Haemophilia is a lifelong bleeding disorder associated with significant morbidity. Because of this for almost 25 years there has been a national network of specialized haemophilia treatment centres (HTCs). Despite this, there is little published information about HTC utilization. We chose to study utilization and satisfaction with care received from the Colorado HTC as compared with that received at other nonspecialized sites. RESEARCH DESIGN: A survey was designed in collaboration between Colorado Department of Public Health and Environment (CDPHE) and the Denver Mountain States Regional Hemophilia Center personnel for telephone administration by CDPHE personnel to all persons with haemophilia (pwh) residing in Colorado in 1994. SUBJECTS: One hundred forty-five persons with haemophilia (77% of those eligible) participated in the survey. RESULTS: The majority of respondents received care from the HTC. Persons less than 21 years of age and those with severe disease were significantly more likely to do so. Satisfaction with care received at the HTC was greater than that received at other sites (P < 0.01). Issues of concern were insurer restricted access to the HTC and the lack of haemophilia knowledge of non-HTC providers. CONCLUSIONS: If HTCs and other specialty centres are to survive in an increasingly managed care environment, in addition to increased patient satisfaction, data documenting improved patient outcome with specialty centre directed care will be necessary to facilitate referral.

Adolescent

Health outcomes as an organisation-wide quality initiative.

Since the burgeoning of the 'health outcomes' movement there has been an ever-increasing body of literature on health outcomes policy debates, directions, frameworks and tools for implementing health outcome-directed initiatives. There is a significant gap in the literature, however, in regard to translating a comprehensive health outcomes policy into practice at a local level. This paper addresses that gap. It describes the local implementation of a comprehensive health outcomes approach which works across the continuum of care. It identifies those organisation-wide structures and processes that support successful progress, thereby providing a useful guide to other organisations wishing to institutionalise the health outcomes approach.

Community Networks

Complete airway obstruction during awake fibreoptic intubation.

Awake fibreoptic intubation is well established as the optimum method of securing the airway in patients in whom difficulty is anticipated. We report a patient undergoing awake fibreoptic intubation in whom the use of topical local anaesthetic precipitated acute loss of the airway so that urgent surgical intervention was required.

Aged

HLA antigens in microscopic polyarteritis (MP) with renal involvement.

Serological HLA-A, B, C, DR and DQ typing was performed in 23 patients with microscopic polyarteritis and renal involvement and in 405 healthy individuals, all of Greek origin. An increased frequency of HLA-A26 (26% vs. 11.3%, x2 = 4.423, p < 0.05) and HLA-A11 (26% vs. 9.6%, x2 = 6.825, P < 0.02), and a decreased frequency of HLA-DR3 (4.3% vs. 24.1%, x2 = 5.935, p < 0.025) were found. Five out of six patients, who did not respond to treatment possessed HLA-DR5. These observations suggest that HLA gene products may influence the clinical expression, as well as the outcome of this disease.

Adolescent

Increased risk in esophageal obstruction with slow-release medications.

Although medication-induced (pill) esophagitis has been recognized for a long time, little data are available on the risk of recently introduced slow-release medications. These formulations may have an obstructive capability (undissolved medication blocking an obstructed lumen) or may cause tissue irritation (continuous leakage from a slowly disintegrating pill). We observed a patient with esophageal carcinoma who developed complete obstruction when three Procardia XL (nifedipine) extended-release tablets blocked the narrowed lumen. An intact Procardia XL tablet and a washed shell as a control were implanted subcutaneously in a rat. The intact pill produced a large inflammatory mass: in contrast, no inflammatory response was noted at the control site implanted with a washed shell. In vitro testing of seven different slow-release medications revealed a wide difference in their solubility at a neutral pH and in gastric juice of pH 1.8 (simulation of esophageal or gastric environment). Theolair-SR (anhydrous theophylline, sustained-release) tablets had the highest obstructive, but no irritating potential. Cardizem SR (diltiazem hydrochloride) sustained-release capsules dissolved promptly without obstructive potential. Adalat CC (nifedipine) extended-release tablets also dissolved early at both pH values. Cardizem CD (diltiazem hydrochloride) extended-release capsules and Calan SR (verapamil hydrochloride) sustained-release oral caplets disintegrated into granules that had a low obstructive potential, but their prolonged presence increased the risk of tissue irritation. Ecotrin (enteric-coated aspirin) tablets had a high obstructive and no irritating potential in the first 24 hours, after which they disintegrated and directly contacted the tissue. Procardia XL extended-release tablets had an insoluble shell that continued to leak a tissue-irritating content even after 48 hours, generating a prolonged obstructive and irritating condition. In conclusion, slow-release medications greatly increase the risk of esophageal injury. Their obstructive and tissue-irritating potentials differ widely. Slow-release formulations should be contraindicated in patients who have obstructive esophageal and gastric disorders.

Aged

The human factor.

Defining the core activity of psychiatric nursing is helpful if the discipline seeks professionalization. A definition offers a sense of stability within the current culture of change in care provision. However, core activity may be incongruent with postmodern ideas and practice. The paper attempts to square this circle. It addresses the complexity of describing core activity when this is based on implicit knowledge of practice, based in art rather than science. Using a phenomenological research approach, the research involved encouraging psychiatric nurses within residential schemes to consider the meaning of their concrete activity. Initial findings suggest that the core activity is working with extraordinary people within 'ordinary' relationships, and in 'ordinary' contexts.

Attitude of Health Personnel

Infections complicating tunneled intraspinal catheter systems used to treat chronic pain.

Tunneled intraspinal catheters and catheter-pump systems are increasingly common treatments for severe chronic pain, but these long-term catheters have caused meningitis, epidural abscesses, and other serious infections. At a cancer referral center, 81 catheters were placed in 72 patients over a 7-year period. There were seven catheter-associated infections: two were meningeal (one was accompanied by an epidural abscess and one by a pocket infection and bacteremia), four were associated with a pocket, and one was associated with a tunnel. The infection rate was 0.77 per 1,000 catheter-days. Pathogenic organisms that were isolated were primarily normal skin flora. By multivariate Cox analysis, the only factor significantly associated with catheter infection was prolonged catheter placement surgery, i.e., a procedure lasting at least 100 minutes (RR, 8.8; 95% CI, 1.6-50). Three patients were cured by removal of the catheter and treatment with antibiotics, and symptoms were satisfactorily suppressed in four patients with antibiotics alone. Considering the severity of illness in catheter recipients, the infection rate was relatively low. Removal of the catheter does not appear mandatory when the goal is suppression of infection-related symptoms, especially when the infection has not spread to the CNS, the infecting organism has an intrinsically low virulence, and the infected patient is terminally ill.

Abscess

Patient adherence to guidelines for diabetes eye care: results from the diabetic eye disease follow-up study.

Early detection and treatment of diabetic eye disease can prevent blindness, yet many persons with diabetes lack regular eye care. This study followed 569 people with diabetes participating in blindness prevention programs during 1985 through 1987; it was found that 35% of subjects received dilated eye examinations before entering the programs, in comparison with 60% afterward. About 85% of participants referred for proliferative retinopathy treatment began such treatment, and, of these, 85% completed treatment. A lack of knowledge about the disease and limited finances were primary reasons for nonadherence. To improve the effectiveness of prevention programs, eye care providers and program staff must strive to eliminate these educational and financial barriers.

Black People

Effect of ursodeoxycholic acid on in vivo and in vitro toxic liver injury in rats.

BACKGROUND: Benefits of ursodeoxycholic acid (UDCA) in cholestatic disorders have been well documented. However, the therapeutic potential of UDCA in parenchymal liver disease is unclear. METHODS: We tested UDCA in rat models of hepatotoxicity: (a) in subacute liver injury induced by repetitive CCl4 and dietary ethyl alcohol (ETH) over seven weeks while receiving oral UDCA; and, (b) in liver slides incubated with CCl4, ETH or p-acetaminophen (APAP) when UDCA was added to the incubating solution. RESULTS: Experiment 1: CCl4 combined with ETH reduced the body weights and resulted in 43% mortality. There was a significant rise in serum ALT, alkaline phosphatase, lipoperoxides (LPO) and in hepatic weight, triglycerides, LPO and histological scores of liver injury. Experiment 2: When liver slides were incubated with hepatotoxins there was an increased transfer of AST and LPO from the tissue into the incubate and a reduction in the valine and thymidine incorporation into the liver proteins or DNA. In none of these situations, whether the liver damage was severe or mild, in vivo or in vitro, UDCA did abolish these hepatotoxic effects. CONCLUSION: In contrast to clinical cholestatic disorders where the reported benefits of UDCA depend on replacement of the accumulated hydrophobic bile acids, these bile acids have a less prominent role in toxic liver injury and UDCA is ineffective.

Acetaminophen

Ursodeoxycholic therapy in chronic liver disease: a meta-analysis in primary biliary cirrhosis and in chronic hepatitis.

OBJECTIVES: to determine whether ursodeoxycholic acid (UDCA) is effective in improving primary biliary cirrhosis (PBC) or chronic hepatitis (CH). METHODS: Meta-analysis (MA) was performed on nine papers and three abstracts describing PBC and on nine papers and two abstracts with CH that were published between 1985 and 1992 and were identified through MEDLINE. Studies were included if they fulfilled established quality criteria and the patients had at least liver histology at the start and two to three relevant laboratory tests repeated after UDCA. A total of 800 patients with PBC were treated for 6-48 months. In CH, 285 patients were treated for 1-21 months. RESULTS: In PBC, an average daily UDCA of 13 mg/kg.day improved the liver tests AST, ALT, ALP, and GGT (all p < 0.001). The effect on serum bilirubin was too heterogeneous to evaluate. When evaluated individually, the studies showed an indeterminate effect on histologic progression and treatment failure. When pooled in MA, UDCA improved the liver histology (p < 0.001) and prevented treatment failure (p < 0.04). In CH, UDCA at an average of 11 mg/kg.day improved AST, ALT, GGT, and total bilirubin (all p < 0.001) and also ALP (p = 0.014). There was no effect on histology of CH and no data on treatment failure. CONCLUSIONS: MA confirmed a beneficial effect of UDCA in PBC on liver tests, histology, and treatment failure. In CH, there was an improvement in liver tests, but the evidence for histologic effect was sparse and insignificant. Future studies in PBC must explore the disease after UDCA is discontinued. Trials in CH should distinguish between the diagnostic subgroups, document patient compliance with UDCA, and include histology and treatment failure as end points.

Hepatitis, Alcoholic

Faculty research productivity in allied health settings: a TQM approach.

Faculty research productivity in colleges of allied health has often been discussed in the literature over the last five years. Articles have focused on the problem of faculty research productivity from various viewpoints, but none have used a theoretical framework to analyze the problem. The total quality management (TQM) framework is currently being used in health care to improve quality and productivity. This article uses the TQM framework to synthesize literature concerning faculty research productivity and verifies the current relevance of synthesis findings using an allied health faculty survey. These analyses show that the TQM framework is useful in suggesting ways to increase faculty research productivity in colleges of allied health.

Allied Health Personnel

Pharmacokinetics of lignocaine in children after infiltration for cleft palate surgery.

We have studied the pharmacokinetics of lignocaine in children after local infiltration for cleft palate surgery. After induction of anaesthesia, lignocaine 2.5 mg kg-1 with adrenaline 1:200,000 was injected into the palate. Blood samples were collected before and at 2, 5, 10, 15, 20, 30, 60 and 120 min after infiltration. Plasma concentrations of lignocaine were measured by a gas-liquid chromatographic technique. There were no signs of systemic toxicity on routine monitoring of the patients and the peak plasma concentrations were less than the accepted toxic values. Mean half-life was 72.9 (SEM 9.9) min, similar to that found previously in adults and children. However differences in mean clearance (24.6 (2.04) ml kg-1 min-1) and volume of distribution (0.80 (0.07) litre kg-1) were found between this and previous studies.

Anesthesia, General