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Biomedical subjects

J Fleming

Publications and source records attributed to J Fleming.

At least 73 records · Page 4Linked to original sources

Network integration: the impact of integrated delivery systems. Roundtable discussion.

One of the hottest, most competitive segments of the healthcare IS industry encompasses integration tools and systems for linking divergent, best-of-breed systems. As firms such as Healthcare Communications, HUBLink, Oacis, Software Technologies Corp., Century Analysis and Eagle Innovations vie for new contracts, CIOs and IS directors wonder about the strategic advantages of single-vendor solutions vs. the best-of-breed approach. This dynamic has driven system acquisitions for several years. More recently, 33 percent of respondents to the 1995 HIMSS/HP Survey cited integration across separate facilities as their No. 1 priority for the next two years. Clearly the emergence of integrated delivery systems and providers of continuums of care--where the cost to replace the information technologies of acquired or partnered entities remains prohibitive--will cause the market for interface engines and other integration tools to continue expanding. Following are the perceptions of a few experts on the topic. They were asked to answer two questions: 1) What are the toughest challenges faced when integrating an integrated delivery system? and 2) What are the current best practices to solving this challenge?

Comprehensive Health Care↗

[Unexplained increase in maternal plasma in alpha-fetoproteins in the second trimester of pregnancy: perinatal results].

To determine the relation between adverse perinatal events and an unexplained mid-trimester elevation in maternal serum alpha-fetoprotein (MSAFP) in an unselected population, 16,093 women with a singleton pregnancy delivered between January 1985 and November 1991, at the Queen Mother's Hospital, Glasgow, Scotland, were studied. The elevated MSAFP group (n = 606) was associated with an increased risk of preterm delivery (odds ratios/95% confidence intervals) (3.7/2.6-5.2), small or gestational age (4.5/3.3-6.1), intrauterine death (3.9/1.7-9.4), and placental abruption (3.2/1.5-6.7). The risks increased with MSAP concentration. An unexplained mid-trimester elevation of MSAFP is associated with increased risk of adverse perinatal events, thus acting as a non-specific marker o a "high risk pregnancy". Alterations to current antenatal management in this group may improve prognosis.

Female↗

Linkage analysis of the whirler deafness gene on mouse chromosome 4.

The whirler mouse harbors an autosomal recessive mutation on mouse chromosome 4 that causes deafness and vestibular dysfunction in the adult that is manifested as head-bobbing and circling behavior. Although there is no obvious human homologue for this mutation as yet, whirler is a potential mouse model for human autosomal recessive deafness. Many genetic markers for this region of mouse chromosome 4 are now available, and we have used these to construct genetic linkage maps in both inter- and intraspecific backcrosses as the first step toward the cloning of the whirler gene. A total of 19 loci were analyzed in these crosses, giving the following gene orders: interspecific cross, centromere-(D4Mit5, D4Mit38)-D4Mit6-(Lv, Tzn, D4Mit44)-wi-Hxb-(D4Mit25, D4Nds9)-(D4Mit7, D4Ler2)-b-D4Mit45-(D4Wsm1, D4Mit27b)-(D4Rck65, D4Mit15), and intraspecific cross, centromere-(Mup-1, wi, Hxb)-b-D4Wsm1. This analysis has positioned the wi locus in the interval between the genes for delta-aminolevulinate dehydratase (Lv) and hexabrachion (Hxb). The human homologues of these genes, ALAD and HXB, both lie on human chromosome 9q32-q34. We therefore predict that a human homologue of the wi gene, involved in autosomal recessive deafness, lies in this region of conserved homology on 9q32-q34.

Animals↗

The selenium metabolite selenodiglutathione induces p53 and apoptosis: relevance to the chemopreventive effects of selenium?

Selenodiglutathione (SDG), the initial metabolite of selenite, is shown to be a more powerful inhibitor of cell growth in vitro than selenite itself. This has been established both with mouse erythroleukaemia (MEL) cells and an ovarian cell line (A2780) which is known to contain wild-type p53. Other seleno-compounds, such as selenomethyl selenocysteine (SMS) and dimethyl selenoxide (DMS), which are potent chemopreventive agents and are known to be metabolized to methylated selenium derivatives directly rather than via SDG, are also growth inhibitory to both MEL and A2780 cells, although less so than SDG or selenite. However, cells growth-inhibited by DMS are more viable than cells growth-inhibited to the same extent by SDG or selenite, suggesting that the methylated seleno-compounds may inhibit cell growth in a different manner from that of SDG or selenite. Our studies of the mechanism of growth inhibition by SDG, have established two facts. First, SDG induces p53 protein levels in cells that contain wild-type p53 (A2780 cells), suggesting that SDG induces the DNA damage-recognition pathway. Secondly, SDG induces apoptosis in MEL cells, as judged by flow cytometry and formation of nucleosomal DNA ladders. However, since p53 mutations have been found to be targetted events in all MEL cells examined, our evidence suggests that induction of apoptosis by SDG is not absolutely dependent on the p53 response pathway.

Animals↗

Dosimetric assessment of radiolabelled lipiodol as a potential therapeutic agent in colorectal liver metastases using combined CT and SPECT.

Lipiodol has previously been used as an agent for targeted radiotherapy by selective retention in primary hepatic tumours following direct hepatic arterial infusion. We have considered the potential dosimetry of 131I-labelled lipiodol in treating colorectal liver metastases. Fifteen patients with multiple colorectal liver metastases underwent selective hepatic angiography when 5 ml lipiodol labelled with 40 MBq 131I were infused. All patients underwent planar scintigraphy of the abdomen and thorax, single photon emission computed tomography (SPECT) of the liver and whole body counting on at least two occasions following lipiodol injection. Computed tomographic (CT) images of the liver were also taken typically 7 days postinjection. The lipiodol was found to deposit on the periphery of metastases of less than 10 cm diameter. In one patient a metastasis of diameter greater than 15 cm failed to infuse. In two patients the lobe of the liver containing metastases was not successfully infused. Overlay of CT and SPECT images confirmed concentration in metastases. Quantification of SPECT images indicated that between 55 and 100% (median 86%) of the injected activity was retained in the liver following injection, and tumour to liver ratios of dose delivered ranged from 1.21:1 to 4.7:1 (median 3.1:1). Tumour does ranged from 11.8 to 43.3 mGy MBq-1 injected. Dose to the lungs ranged from 0 to 46% of the liver dose (median 16%). Lipiodol has potential for treatment of colorectal liver metastases in targeted radiotherapy.

Colonic Neoplasms↗

The missing variable: ensuring a positive ROI (return on investment).

In summary, the business value of IS technology is a function of its role in the organization's business strategy. Value can be assigned to expected benefits from the technology. But, the validity of that determination depends on developing a plan to fully and appropriately use the technology, reengineer operations and embrace a new way of doing business. The need for IS technology in today's healthcare environment is unquestioned. Realizing the full business value of IS technology is the issue. Will it be treated as an expense to be minimized, or as a strategy for the future? A strategy embraced as part of the new evolving healthcare delivery system will result in your investment in IS technology truly being an investment in the future.

Capital Expenditures↗

Analysis of the Pax-3 gene in the mouse mutant splotch.

In a linkage analysis of Pax-3 and splotch no recombinations were found in 117 backcross mice. Molecular analysis of Pax-3 in three alleles of splotch shows a number of significant alterations to the Pax-3 gene. In Sp/Sp embryos, cDNA PCR analysis reveals a shortened transcript in which exon 4 of Pax-3 is deleted due to mutation of the splice acceptor site of intron 3. In the Sp4H allele, the Pax-3 gene is deleted and in Spd embryos, Pax-3 expression is significantly lower than that in normal littermate embryos. The linkage analysis, shortened Pax-3 transcript in Sp, and deletion of Pax-3 in Sp4H described here, together with the previous report of an intragenic deletion in Pax-3 in Sp2H mice and the deletion of Pax-3 in Spr mice, provide strong evidence for the allelic identity of Pax-3 and Sp.

Alleles↗

Predictors of postoperative respiratory complications in premature infants after inguinal herniorrhaphy.

There is a significant incidence of inguinal hernia in premature infants and the optimal timing of repair is controversial. A high rate of postoperative respiratory complications has been reported in this group. In this study, the records of 47 premature infants (mean gestational age, 30.3 weeks) who underwent herniorrhaphy while still in the neonatal intensive care unit were reviewed in an effort to define those conditions that are independent risk factors for complications. Forty-three percent of infants had complications, including postoperative assisted ventilation (34%), episodes of apnea and/or bradycardia (23%), emesis and cyanosis with first feeding (6%), and requirement for postoperative reintubation (4%). Although low gestational age and postconceptual age at operation, low birth weight for gestational age, and preoperative ventilatory assistance were significantly associated with postoperative complications, only a history of respiratory distress syndrome/bronchopulmonary dysplasia (odds ratio 2.3), a history of patent ductus arteriosus (odds ratio 2.5), and low absolute weight at operation (odds ratio 3.5 for 1,000-g decrease) were independent risk factors for postoperative complication. Despite previous reports citing postconceptual age as the factor having the greatest impact on postoperative complications, these results indicate that a history of respiratory dysfunction and size at operation may be more important predictors of postoperative respiratory dysfunction in preterm infants.

Age Factors↗

Different patterns of regulation of the genes encoding the closely related 56 kDa selenium- and acetaminophen-binding proteins in normal tissues and during carcinogenesis.

A full-length cDNA encoding a 56 kDa liver protein recently implicated in the detoxification of acetaminophen (AP56) has been cloned by virtue of its similarity to the 56 kDa selenium-binding protein (SP56): in fact, the deduced AP56 amino acid sequence differs at only 14 residues from SP56. Isolation of genomic DNA recombinants from a Balb/c mouse cosmid genomic DNA library shows that SP56 and AP56 are encoded by two different genes. Using reverse transcription/PCR with oligonucleotide primers that distinguish the AP56 and SP56 mRNAs shows that the SP56 mRNA is highly expressed in liver, kidney and, to a lesser extent, lung; whereas the AP56 mRNA is mainly expressed in liver. Both mRNAs tend to be down-regulated in liver cell lines but remain high in DEN-induced liver tumours in vivo. The relevance of these findings is evaluated in terms of the postulated functions of the two proteins in mediating the anti-carcinogenic effects of selenium and detoxification mechanisms.

Acetaminophen↗

The epidemiology of HIV-1 infection of the lung in AIDS patients.

OBJECTIVE: To examine the relationship between HIV-1 infection of cells obtained by bronchoalveolar lavage (BAL) from the lung and the pathogenesis of AIDS. DESIGN: Prospective study of 121 consecutive HIV-1-seropositive patients undergoing investigation for respiratory symptoms or abnormal chest radiograph. METHODS: Polymerase chain reaction (PCR) for the detection of HIV-1-specific proviral DNA. Cocultivation of leukocytes obtained from BAL with donor cord blood leukocytes (CBL) to isolate HIV-1. RESULTS: HIV-1 was detected by PCR in the lung cells of 78 out of 121 (65%) patients. It was detected in 55% of patients who had been seropositive for less than 1 year, but in over 80% of patients who had been seropositive for more than 3 years. HIV-1 was isolated from 61 out of 106 (58%) individuals. The ability to detect or isolate HIV-1 from the lung correlated directly to CD4 cell count in peripheral blood. HIV-1 was detected significantly more frequently in the BAL cells of smokers compared with non-smokers (P = 0.01). CONCLUSIONS: HIV-1 was frequently detected and isolated from the lung of AIDS patients undergoing a respiratory episode. HIV-1 infection of the lung became more frequent with time from serodiagnosis. Patients who smoked were more likely to succumb to HIV-1 infiltration into the lung and HIV-1 infection of the lung was associated with progression to death.

Adult↗

The effect of cigarette smoking on the development of AIDS in HIV-1-seropositive individuals.

OBJECTIVE: To determine whether HIV-1-seropositive cigarette smokers progress more rapidly to AIDS than HIV-1-seropositive non-smokers. SETTING: The genitourinary medicine outpatient department of St Mary's Hospital, London, which is a London University teaching hospital (tertiary care centre). SUBJECTS AND DESIGN: Case series of 84 individuals with AIDS who provided accurate details of their smoking habits before their AIDS-defining diagnosis. MAIN OUTCOME MEASURE: Progression time to AIDS in relation to smoking habit. RESULTS: Progression time to AIDS (all diagnoses) was significantly reduced in HIV-1-seropositive smokers: median time to AIDS was 8.17 months for smokers (n = 43) and 14.50 months for non-smokers (n = 41) (P = 0.003). Smokers developed Pneumocystis carinii pneumonia (PCP) more rapidly than non-smokers, with a median time to PCP of 9.0 months, compared with 16.0 months for non-smokers (P = 0.002). Smoking had no significant effect on progression time to AIDS when not due to PCP. CONCLUSION: Cigarette smoking by HIV-1-seropositive individuals is associated with a more rapid development of AIDS and should be discouraged.

Acquired Immunodeficiency Syndrome↗

Relation of HIV-I in bronchoalveolar lavage cells to abnormalities of lung function and to the presence of Pneumocystis pneumonia in HIV-I seropositive patients.

BACKGROUND: HIV is present in bronchoalveolar lavage cells of some but not all HIV seropositive patients. Abnormalities of lung function have been described in such patients in the absence of clinically overt pneumonia or other respiratory infections. It is possible that the presence of HIV in alveolar macrophages could account for these abnormalities. It is also possible that the presence of HIV in alveolar macrophages contributes to immunosuppression and an increased incidence of opportunistic infections. METHODS: This was a prospective study of 157 HIV seropositive patients requiring diagnostic bronchoscopy for investigation of new respiratory symptoms, chest radiograph abnormality, or pneumonic illness. Presence of HIV in bronchoalveolar lavage cells obtained at diagnostic bronchoscopy was determined by polymerase chain reaction to detect proviral DNA and in vitro cocultivation to detect productive virus infection. With these two techniques the presence or absence of HIV in bronchoalveolar lavage was compared with the presence of abnormalities of lung function or presence of Pneumocystis pneumonia. RESULTS: HIV was detected in bronchoalveolar lavage cells in 65% of patients by means of the polymerase chain reaction and 59% with cocultivation. With both methods of detection there was no association between the presence or absence of HIV and the presence of Pneumocystis pneumonia; nor was there a relation between the presence of HIV and abnormalities of lung function. CONCLUSION: The presence of HIV in bronchoalveolar lavage cells does not predispose to an increased incidence of Pneumocystis pneumonia; nor does it contribute to abnormalities of lung function.

Bronchoalveolar Lavage Fluid↗

Reduced carbon monoxide transfer factor (TLCO) in human immunodeficiency virus type I (HIV-I) infection as a predictor for faster progression to AIDS.

BACKGROUND: In addition to the acute fall in carbon monoxide transfer factor (TLCO) associated with Pneumocystis carinii pneumonia (PCP) or other opportunistic lung infections, reduced TLCO occurs in HIV-I seropositive individuals without active pulmonary disease. Abnormal TLCO, in the absence of lung disease, may be a surrogate marker of HIV-I induced immunosuppression and, therefore, a predictor for a more rapid progression to AIDS. METHODS: Eighty four individuals with AIDS, who had regular pulmonary function tests before the diagnosis of AIDS was made, were identified from a cohort of patients with HIV-I infection. None had evidence of active pulmonary disease at the time of initial pulmonary function testing. The relation between the time taken to progress to AIDS and initial pulmonary function tests was examined with life table survival analysis. RESULTS: Patients with a TLCO value of < 80% of predicted normal (n = 46) progressed significantly faster to AIDS, with a median time of 8.0 months compared with 16.5 months for those with a TLCO value of > or = 80% (n = 38). When stratified by AIDS defining diagnosis (PCP or non-PCP), median time to PCP was also significantly related to initial TLCO values (TLCO of < 80% = 9.0 months, TLCO of > or = 80% = 19.0 months). Reductions in other measurements of lung function (FEV1, FVC, KCO) were not temporally associated with the development of AIDS. CONCLUSIONS: HIV-I seropositive individuals with TLCO values of < 80% predicted and no evidence of lung disease progress more rapidly to AIDS than those with TLCO values of > or = 80%.

Acquired Immunodeficiency Syndrome↗

Nursing specialty practice guidelines: the implications for clinical scholarship and early intervention practice. American Nurses' Association.

Specialty practice guidelines provide the nursing profession with the opportunity to examine, document, and revise practice, thus contributing to clinical scholarship and nursing science. The development and evaluation of one particular specialty practice guideline, the Children with Special Health Care Needs Guidelines, and the implications for early intervention practice are described. Recommendations for clinical research and usage for the Education of the Handicapped Act Amendment of 1986 (Public Law 99-457) are included.

Child↗