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Biomedical subjects

R Stevens

Publications and source records attributed to R Stevens.

At least 73 records · Page 4Linked to original sources
PubMed1998

In vitro and in vivo antifungal activity of amphotericin B lipid complex: are phospholipases important?

Amphotericin B lipid complex for injection (ABLC) is a suspension of amphotericin B complexed with the lipids L-alpha-dimyristoylphosphatidylcholine (DMPC) and L-alpha-dimyristoylphosphatidylglycerol. ABLC is less toxic than amphotericin B deoxycholate (AmB-d), while it maintains the antifungal activity of AmB-d. Active amphotericin B can be released from ABLC by exogenously added (snake venom, bacteria, or Candida-derived) phospholipases or by phospholipases derived from activated mammalian vascular tissue (rat arteries). Such extracellular phospholipases are capable of hydrolyzing the major lipid in ABLC. Mutants of C. albicans that were resistant to ABLC but not AmB-d in vitro were deficient in extracellular phospholipase activity, as measured on egg yolk agar or as measured by their ability to hydrolyze DMPC in ABLC. ABLC was nevertheless effective in the treatment of experimental murine infections produced by these mutants. Isolates of Aspergillus species, apparently resistant to ABLC in vitro (but susceptible to AmB-d), were also susceptible to ABLC in vivo. We suggest that routine in vitro susceptibility tests with ABLC itself as the test material may not accurately predict the in vivo activity of ABLC and that the enhanced therapeutic index of ABLC relative to that of AmB-d in vivo may be due, in part, to the selective release of active amphotericin B from the complex at sites of fungal infection through the action of fungal or host cell-derived phospholipases.

Amphotericin B↗
PubMed1998

Predictors of success within a behavior modification program among male adolescents.

48 adolescents placed into a short-term diagnostic group home with a behavior modification program in place were studied. Each subject was administered the Wechsler Intelligence Scale for Children--III and the Screener version of the Wechsler Individual Achievement Test. Assessment data were used to predict the subjects' conduct within the behavioral program as a method of strengthening pretreatment recommendations for planning. Analysis showed that verbal and mathematical skills were significant predictors of the criterion behaviors. These results support the use of cognitive assessment as valid methods of predicting the behavior of teenagers within residential behavior modification programs.

Adolescent↗
PubMed1998

TAMBIS--Transparent Access to Multiple Bioinformatics Information Sources.

The TAMBIS project aims to provide transparent access to disparate biological databases and analysis tools, enabling users to utilize a wide range of resources with the minimum of effort. A prototype system has been developed that includes a knowledge base of biological terminology (the biological Concept Model), a model of the underlying data sources (the Source Model) and a 'knowledge-driven' user interface. Biological concepts are captured in the knowledge base using a description logic called GRAIL. The Concept Model provides the user with the concepts necessary to construct a wide range of multiple-source queries, and the user interface provides a flexible means of constructing and manipulating those queries. The Source Model provides a description of the underlying sources and mappings between terms used in the sources and terms in the biological Concept Model. The Concept Model and Source Model provide a level of indirection that shields the user from source details, providing a high level of source transparency. Source independent, declarative queries formed from terms in the Concept Model are transformed into a set of source dependent, executable procedures. Query formulation, translation and execution is demonstrated using a working example.

Artificial Intelligence↗
PubMed1997

Enhancement of the in vivo circulation lifetime of L-alpha-distearoylphosphatidylcholine liposomes: importance of liposomal aggregation versus complement opsonization.

Incorporation of N-(omega-carboxy)acylamido-phosphatidylethanolamines (-PEs) into large unilamellar vesicles (LUVs) of L-alpha-distearoylphosphatidylcholine (DSPC) was found to dramatically increase the in vivo liposomal circulation lifetime in rats, reaching a maximal effect at 10 mol.% of the total phospholipid. Neither pure DSPC liposomes nor those with the longest circulating derivative, N-glutaryl-dipalmitoylphosphatidylethanolamine (-DPPE), were found to significantly bind complement from serum. Therefore, the relatively short circulation time of pure DSPC liposomes did not appear to be related to greater complement opsonization leading to uptake by the reticuloendothelial system. However, N-(omega-carboxy)acylamido-PEs were particularly efficient inhibitors of a limited aggregation detected for pure DSPC liposomes. The aggregation tendency of DSPC liposomes incorporating various structural analogs of N-glutaryl-DPPE correlated inversely with the circulation lifetimes. Therefore, it is concluded that such PE derivatives enhance the circulation time by preventing liposomal aggregation and avoiding a poorly understood mechanism of clearance that is dependent on size but is independent of complement opsonization. At high concentrations of N-glutaryl-DPPE (above 10 mol.%), the liposomes exhibited strong complement opsonization and were cleared from circulation rapidly, as were other highly negatively charged liposomes. These data demonstrate that both the lack of opsonization and the lack of a tendency to aggregate are required for long circulation. Liposomal disaggregation via N-(omega-carboxy)acylamido-PEs yields a new class of large unilamellar DSPC liposomes with circulation lifetimes that are comparable to those of sterically stabilized liposomes.

Amino Acids↗
PubMed1997

Recurrent branch retinal infarcts in association with migraine.

Migraine has been blamed for a variety of temporary and permanent visual complications. We describe the case of a young woman with migraine who suffered recurrent episodes of retinal infarction, one of which occurred during an attack of migraine. The infarctions resulted from occlusions of branches of the central retinal artery. Extensive laboratory and radiological investigations failed to establish a nonmigrainous etiology. In some individuals, migraine may cause or promote branch retinal vaso-occlusion and infarction.

Adult↗
PubMed1997

Relationship of serotype, leukotoxin gene type and lysogeny in Actinobacillus actinomycetemcomitans to periodontal disease status.

Actinobacillus actinomycetemcomitans has been associated with different forms of periodontitis, particularly with localized juvenile periodontitis (LJP). The bacterium possesses several virulence factors which have been shown to interact with the host immune system. Among these factors, leukotoxin, surface antigens (serotype) and bacteriophages have been suggested directly or indirectly to influence the course of infection. However, few studies have been able to show associations between these factors and periodontal disease, alone or in combination. Thus, the purpose of the present study was to investigate possible correlations between periodontal disease status and selected virulence factors (serotype, presence of bacteriophages, and the presence of a 530 bp deletion in the promoter region of the leukotoxin gene). 36 subjects took part in the study. Serotype c was the most frequently found serotype among periodontally affected subjects, although serotypes a and b were also present. 27 out of 36 strains harbored bacteriophages, and there was strong evidence that some of the bacteriophages were different from the previously characterized phi Aa phage. A. actinomycetemcomitans containing the F-fragment phage were more frequently associated with periodontal disease. Five strains, all serotype b, 3 from LJP patients and 2 from healthy subjects, showed a 530-bp deletion in the promoter region of the leukotoxin gene.

Actinobacillus Infections↗
PubMed1997

Field immobilization of muskrats (Ondatra zibethicus) for minor surgical procedures.

A combination of ketamine hydrochloride and xylazine hydrochloride at doses of 50 mg/kg and 5 mg/kg, respectively, was used to immobilize 48 muskrats (Ondatra zibethicus) from October 1993 to November 1994 in Tennessee (USA). Mean (+/-SD) time for induction was 2.97 +/- 1.1 min. After a mean (+/-SD) duration of 27.2 +/- 3.5 min intramuscular yohimbine hydrochloride at a dose of 0.125 mg/kg was administered. Mean (+/-SD) recovery time was 48.1 +/- 21.6 min. All anesthetic inductions were smooth and sufficient depth of anesthesia was achieved to allow surgical collection of adipose tissue. Recovery times were more variable than expected. There was a significant (P < or = 0.05) drop in heart rate, respiratory rate, and body temperature during anesthesia. One animal died during recovery.

Anesthetics, Dissociative↗
PubMed1996

Linking clinical and public health approaches to improve access to health care for socially disadvantaged mothers and children. A feasibility study.

OBJECTIVE: To test the feasibility of combining home- and office-based interventions to improve access to health care and health outcomes of Medicaid-eligible mothers and infants. DESIGN: Randomized trial in 2 counties in North Carolina (1 rural, 1 urban). Information on health and developmental outcomes was obtained by face-to-face interviews, medical chart abstractions, hospital medical records, and state data tapes. PARTICIPANTS: Ninety-three Medicaid-eligible first-time pregnant women in their third trimester and their subsequently born infants, who were followed up until they were 6 months old, and 3 pediatric practices and 1 family practice. INTERVENTIONS: Coordinated home visit and office intervention, office intervention, and usual care. Home visits by 3 public health nurses provided parental education and social support and linked families with needed community resources. Women in the office intervention group were encouraged to seek health care for their infants from one of the primary care practices. Participating offices received assistance with Medicaid billing, help developing a system to improve preventive care, and customized patient education materials. RESULTS: Mothers reported that the nurses helped them in areas related to the content of the program. An office system for prevention was developed and implemented in all 4 practices for study patients. Families in the intervention groups were more likely than control families to have had a prenatal visit with a pediatrician (P = .01, chi 2), a primary care office as the regular source of sick care (P = .02, chi 2), and less waiting time (P = .02, Student t test). They were also more likely to recall receiving patient education materials (P = .007, chi 2). CONCLUSIONS: It is feasible to link clinical and public health approaches to improve the quality and effectiveness of care for socially disadvantaged children. Such interventions should be tested in defined populations.

Child Health Services↗
PubMed1996

Manipulation of glutathione metabolism in transgenic plants.

There is clear potential for the genetic manipulation of key enzymes involved in stress metabolism in transgenic plants. However, the data emerging so far from such experiments are equivocal. The detailed analysis of stress responses in progeny of primary transgenics, coupled with comparisons with control transgenic plants that do not contain the GR transgene, allows us to take into account the possible variation in response to stress associated with regeneration of plants from tissue culture. The picture that is now beginning to emerge with respect to the role of GR in stress protection is that, although there are clearly benefits to be had from overexpression of the enzymes, there is no direct correlation between enzyme levels and stress tolerance. It may be that overexpression of the cytosolic isoform (gor2) will prove to be of greater benefit. Furthermore, the types of stresses to which transgenic plants have been exposed in order to assess the consequences of oxidative stress tolerance cannot reproduce those that will experienced in field conditions. Only when plants with higher GR levels and increased glutathione synthesis capacity are grown in field trials will it be possible to make a full assessment of the benefits of engineering plants with altered glutathione metabolism.

Amino Acid Sequence↗
PubMed1996

Noonan syndrome: coagulation and clinical aspects.

The study aims were to review the clinical features of a group of patients with Noonan syndrome and to further elucidate their bleeding tendency. Eighteen patients (12M, 6F) aged 2.6-13.3 years underwent a clinical assessment, a questionnaire of their bleeding tendency and laboratory coagulation studies. Nine had cyanotic spells or breathing difficulties after birth; 11 had poor feeding or weight gain. Increased bruising or bleeding was reported in 12 (67%), four of whom had bleeding from the oral cavity. Excessive bleeding was not reported from operative procedures in other sites. Partial thromboplastin time was prolonged in 10 (56%) associated with low levels of clotting factors, particularly XI and XII. Bleeding times were normal; one had marginal thrombocytopenia. Coagulation results did not correlate with bruising history and may not predict bleeding risk. Care is required when Noonan syndrome patients undergo surgery, particularly of the oropharynx, with immediate availability of suitable blood products.

Adolescent↗
PubMed1996

Access to care: a home visitation program that links public health nurses, physicians, mothers, and babies.

The purpose of the project here was to develop and test interventions designed to improve access to care and health outcomes for Medicaid-eligible infants during their first 6 months of life. The goal of the intervention was to overcome personal and structural barriers to care by combining the efforts of county health departments and private physicians' offices in 2 counties in North Carolina. The project combined home visits and an office intervention.

Feasibility Studies↗
PubMed1996

Quinolones: a practical review of clinical uses, dosing considerations, and drug interactions.

A review of the literature on quinolones reveals numerous clinically relevant points regarding indications, dosing considerations, and drug interactions. Quinolones are useful in the treatment of several infectious diseases. Unfortunately, indiscriminate use of these valuable antimicrobials has resulted in increased patterns of resistance. It is important to consider carefully the site of infection and the potential pathogens in each patient before dosing. Quinolones have excellent oral absorption, with peak serum concentrations approaching those achieved with intravenous administration. When prescribing quinolones, the dose should be based on estimated creatinine clearance. Quinolones are associated with several clinically significant drug interactions. Some of these agents are well-documented inhibitors of hepatic metabolism of theophylline, caffeine, and warfarin. It has been well documented that divalent and trivalent cations in antacids, sucralfate, and some other products significantly reduce the absorption of quinolones. Avoidance or proper management of these interactions is required to ensure optimal safety and efficacy.

Anti-Infective Agents↗
PubMed1995

[Cardiac surgery in octogenarians].

37 patients aged 80 or over underwent cardiac surgery during an 11-year period. Operative indications included angina, dyspnea and syncope. The majority of patients (n = 32) had a left ventricular ejection fraction greater than 0.5. There were 28 aortic valve procedures, of which seven were combined with coronary artery bypass grafts (CABG), and 2 with mitral valve repair; in addition, 7 isolated CABG procedures and one isolated mitral valve repair were performed. 36-day mortality was 5.4% (2 patients); 9 patients died at a later date (2.5 to 118 months after surgery). The most frequent postoperative complications were atrial fibrillation, pulmonary infection or atelectasis, transient delirium and atrioventricular conduction disturbances. Mean hospital stay was 14.5 days. 1- and 5-year actuarial survival rates were 83% and 57%. In a control group of patients aged 60-69 matched for preoperative characteristics, there were no in-hospital fatalities and 1- and 5-year survival were, respectively, 100% and 82%. Among complications, only conduction disturbances and transient delirium were significantly more frequent in the octogenarian group. At follow-up, the proportion of severely symptomatic octogenarians had diminished to 24% from 84%. In conclusion, cardiac surgery can be performed on octagenarians with adequate myocardial reserve, exposing them to a perioperative mortality that is in the range of younger age groups while offering an equivalent prospect for functional improvement.

Age Factors↗
PubMed1995

HIV infection suppresses type 1 lymphokine and IL-12 responses to Toxoplasma gondii but fails to inhibit the synthesis of other parasite-induced monokines.

Individuals infected with Toxoplasma gondii normally develop resistance to the parasite, resulting in an asymptomatic chronic infection. In AIDS patients, this resistance is lost leading to reactivation of infection and development of encephalitis. To characterize the cytokine response of T. gondii-infected individuals, PBMC were cultured in vitro in the presence or absence of crude tachyzoite Ags (STAg). When stimulated with STAg, PBMC from T. gondii-infected donors, but not controls, produced high levels of Type 1 lymphokines (IL-2 and IFN-gamma) as well as the monokine IL-12, in the absence of detectable Type 2 lymphokines (IL-4 and IL-5). In contrast, cells of individuals from both groups produced high levels of IL-1, IL-6, and TNF-alpha when exposed to the same Ag preparation. By using highly purified elutriated cells, we demonstrated that monocytes are a major source of these monokines. The above findings were further expanded by analyzing the cytokine responses induced by STAg in PBMC from patients co-infected with T. gondii and HIV. Our results demonstrate that parasite-specific IL-2 and IFN-gamma responses are greatly impaired even before AIDS development, as is IL-12 synthesis by PBMC from HIV-infected individuals stimulated with STAg. In contrast, the release of IL-6 and TNF-alpha triggered by STAg is either not affected or augmented during HIV infection.

AIDS-Related Opportunistic Infections↗