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Biomedical subjects

P Johnson

Publications and source records attributed to P Johnson.

At least 73 records · Page 4Linked to original sources
PubMed2000

A phase II study of gemcitabine plus oral etoposide in the treatment of patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: The authors have designed a non-cisplatin-based chemotherapy regimen for the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC). This regimen capitalizes on the mild toxicity of gemcitabine, a novel nucleoside analog. METHODS: A total of 46 chemotherapy-naive patients with histologically confirmed Stage IIIB or IV NSCLC were enrolled. Eligible patients were treated with gemcitabine 1000 mg/m(2) on Days 1, 8, and 15, plus oral etoposide 50 mg daily for 14 days, which was increased to 21 days if there was no World Health Organization (WHO) Grade 3 or 4 toxicity in the 1st 2 cycles (each cycle was 28 days long). All patients were included for analysis of response and survival according to an intention-to-treat principle. RESULTS: The overall response rate was 43.5% (95% confidence interval [CI], 30. 7-60.2%). There was 1 complete response (2.2%) and 19 partial responses (41.3%). The median survival was 48.0 weeks (95% CI, 38. 1-75.9 weeks) and the 1-year survival rate was 45% (95% CI, 29-62%). The median time to progression for all patients was 39.2 weeks (95% CI, 35.7-49.7 weeks). World Health Organization (WHO) Grade 3 and 4 anemia, neutropenia, and thrombocytopenia was reported in 29%, 32%, and 18% of patients, respectively. Two patients had reactivation of hepatitis B viral infection that resulted in WHO Grade 4 hepatic dysfunction. Other nonhematologic toxicities were uncommon. CONCLUSIONS: This non-cisplatin-based regimen of gemcitabine and oral etoposide achieved a high response and survival rate. Toxicity appeared to be less severe than that associated with existing cisplatin-based regimens. A randomized study of this regimen versus a cisplatin-based regimen is indicated.

Adult↗
PubMed2000

Medicaid and indigent care issue brief: Medicaid: access to health services.

Medicaid provides health insurance coverage to low-income children, parents meeting specific income thresholds, pregnant women, the elderly and people with disabilities. According to the U.S. Census Bureau, Medicaid provided health insurance for approximately 14 million people in 1998. In that same year, however, 11.2 million poor people had no health insurance at all. In order to reduce the number of people without health insurance, states have expanded or clarified their eligibility standards to allow more people to enroll in Medicaid.

Forecasting↗
PubMed2000

Medicaid and indigent care issue brief: Medicaid: managed care.

In an effort to reduce the high cost of fee-for-service health care, many states have implemented managed care into their Medicaid programs. Managed care has many forms, but the most traditional measures states adopt are fully capitated, partially capitated, or primary care case management (PCCM) programs. According to the Kaiser Commission on the Future of Medicaid, enrollment in Medicaid managed care has grown dramatically from 2.7 million beneficiaries in 1991 to 16.6 million in 1998. Over half (53.6 percent) of Medicaid beneficiaries, predominately poor children and their parents, are enrolled in some form of managed care.

Humans↗
PubMed2000

Medicaid and indigent care issue brief: Medicaid: services covered.

Medicaid provides health care insurance for low-income children, some parents who meet income thresholds, pregnant women, the elderly and the disabled. In order to receive federal funds for Medicaid, each state must offer coverage for the following health care services: inpatient and outpatient hospital services; physician services; medical and surgical dental services; nursing facility services; home health care services; family planning services; rural health clinic services; laboratory and x-ray services; pediatric and family nurse practitioner services; federally qualified health center services; nurse-midwife services; and early and periodic screening, diagnosis and treatment (EPSDT) services for individuals under age 21. States can also choose to cover certain additional services under their Medicaid plans, and these often include prescription drugs, dental services (nonmedical or surgical), clinic services, and vision and hearing services. It is up to each state to decide what optional services to include with the mandated services to create their Medicaid benefit package.

Forecasting↗
PubMed2000

Medicaid and indigent care issue brief: Medicaid: provider reimbursement.

Medicaid provider reimbursement rates have been a hot topic for the last several years. States including California, Hawaii, Indiana, Maryland and Mississippi addressed the issue in the 1999 legislative session and 37 states have identified Medicaid provider reimbursement as a legislative priority for 2000.

Forecasting↗
PubMed2000

Medicaid and indigent care issue brief: state response to children's health insurance programs.

According to recent Census Bureau data, approximately 11.1 million children (people less than 18 years of age) were uninsured in 1998. Many of these children are in families with working parents who either do not receive health care coverage through their employers or cannot afford coverage through private sources. Uninsured children are less likely to visit a physician routinely, get care for injuries or have a regular source of health care. This link between health insurance and access to health care makes the increasing number of uninsured children a serious problem not only for children, but for society as a whole. Most states intend to subsidize children's health insurance with federal funding provided by the Balanced Budget Act of 1997. The Balanced Budget Act provides enhanced federal funding to states that create plans to provide coverage to targeted children from low-income families. Uninsured children already were high on state agendas before passage of this law, but now, with new federal funds, many states are taking action to cover their most vulnerable citizens.

Adolescent↗
PubMed2000

Medicaid and indigent care issue brief: Medicaid: provider reimbursement.

Medicaid provider reimbursement rates have been a hot topic for the last several years. States including California, Hawaii, Indiana, Maryland and Mississippi addressed the issue in the 1999 legislative session and 37 states have identified Medicaid provider reimbursement as a legislative priority for 2000.

Forecasting↗
PubMed2000

Medicaid and indigent care issue brief: Medicaid: services covered.

Medicaid provides health care insurance for low-income children, some parents who meet income thresholds, pregnant women, the elderly and the disabled. In order to receive federal funds for Medicaid, each state must offer coverage for the following health care services: inpatient and outpatient hospital services; physician services; medical and surgical dental services; nursing facility services; home health care services; family planning services; rural health clinic services; laboratory and x-ray services; pediatric and family nurse practitioner services; federally qualified health center services; nurse-midwife services; and early and periodic screening, diagnosis and treatment (EPSDT) services for individuals under age 21. States can also choose to cover certain additional services under their Medicaid plans, and these often include prescription drugs, dental services (nonmedical or surgical), clinic services, and vision and hearing services. It is up to each state to decide what optional services to include with the mandated services to create their Medicaid benefit package.

Delivery of Health Care↗
PubMed2000

Stable interdomain interaction within the cytoplasmic domain of CD45 increases enzyme stability.

CD45 is a leukocyte-specific, two domain transmembrane tyrosine phosphatase. Co-purification of a recombinant protein containing the first phosphatase domain of CD45 (6His-D1) with a recombinant protein containing the second phosphatase domain (GST-D2) from E. coli indicated a stable interaction which resulted in increased stability of the active phosphatase domain present in 6His-D1. This interaction was not dependent on the acidic region unique to CD45 domain 2, but was affected by a destabilizing point mutation (Q1180G) in GST-D2. CD45 domain 2 enhanced phosphatase activity of the first domain in the full length cytoplasmic domain protein, whereas a chimeric protein with the SH2 domain of p56(lck) in place of the CD45 C-terminal region did not. Thus the C-terminal domain of CD45 associates with the N-terminal domain and this stabilizes the active phosphatase domain. A single destabilizing point mutation in the second domain is sufficient to attenuate this effect.

Animals↗
PubMed2000

Practice guidelines for the management of patients with histoplasmosis. Infectious Diseases Society of America.

OBJECTIVE: The objective of this guideline is to provide recommendations for treating patients with the more common forms of histoplasmosis. PARTICIPANTS AND CONSENSUS PROCESS: A working group of 8 experts in this field was convened to develop this guideline. The working group developed and refined the guideline through a series of conference calls. OUTCOMES: The goal of treatment is to eradicate the infection when possible, although chronic suppression may be adequate for patients with AIDS and other serious immunosuppressive disorders. Other important outcomes are resolution of clinical abnormalities and prevention of relapse. EVIDENCE: The published literature on the management of histoplasmosis was reviewed. Controlled trials have been conducted that address the treatment of chronic pulmonary and disseminated histoplasmosis, but clinical experience and descriptive studies provide the basis for recommendations for other forms of histoplasmosis. VALUE: Value was assigned on the basis of the strength of the evidence supporting treatment recommendations, with the highest value assigned to controlled trials, according to conventions established for developing practice guidelines. BENEFITS AND COSTS: Certain forms of histoplasmosis cause life-threatening illnesses and result in considerable morbidity, whereas other manifestations cause no symptoms or minor self-limited illnesses. The nonprogressive forms of histoplasmosis, however, may reduce functional capacity, affecting work capacity and quality of life for several months. Treatment is clearly beneficial and cost-effective for patients with progressive forms of histoplasmosis, such as chronic pulmonary or disseminated infection. It remains unknown whether treatment improves the outcome for patients with the self-limited manifestations, since this patient population has not been studied. Other chronic progressive forms of histoplasmosis are not responsive to pharmacologic treatment. TREATMENT OPTIONS: Options for therapy for histoplasmosis include ketoconazole, itraconazole, fluconazole, amphotericin B (Fungizone; Bristol-Meyer Squibb, Princeton, NJ), liposomal amphotericin B (AmBisome; Fujisawa, Deerfield, IL), amphotericin B colloidal suspension (ABCD, or Amphotec; Seques, Menlo Park, CA), and amphotericin B lipid complex (ABLC, or Abelcet; Liposome, Princeton, NJ).

Antifungal Agents↗
PubMed2000

A role for the cell adhesion molecule CD44 and sulfation in leukocyte-endothelial cell adhesion during an inflammatory response?

CD44 is a widely expressed cell adhesion molecule that has been implicated in a variety of biological processes including lymphopoiesis, angiogenesis, wound healing, leukocyte extravasation at inflammatory sites, and tumor metastasis. The adhesive function of CD44, like other molecules involved in inducible adhesion, is tightly regulated. Post-translational modifications, isoform expression, aggregation state, and protein associations all can affect the ligand binding properties of CD44, and these can vary depending on the cell type and the activation state of the cell. The most extensively characterized ligand for CD44 is hyaluronan, a component of the extracellular matrix. Interactions between CD44 and hyaluronan can mediate both cell-cell and cell-extracellular matrix adhesion. In the immune system, both the selectin molecules and CD44 have been implicated in the initial binding of leukocytes to endothelial cells at an inflammatory site. Sulfation is required for selectin-mediated leukocyte-endothelial cell interactions, and, recently, inducible sulfation also was shown to regulate CD44-mediated leukocyte adhesion to endothelial cells. Sulfation, therefore, may be important in the regulation of cell adhesion at inflammatory sites. In this commentary we have reviewed the molecular aspects of CD44 and the mechanisms that regulate its binding to hyaluronan. In addition, we have summarized the role of CD44 and hyaluronan in mediating leukocyte-endothelial cell interactions and have discussed how this interaction may be regulated. Finally, we examined the potential role of sulfation as an inducible means to regulate CD44-mediated leukocyte adhesion and as a more general mechanism to regulate leukocyte-endothelial cell interactions.

Animals↗
PubMed2000

Apparent confined placental mosaicism of trisomy 16 and multiple fetal anomalies: case report.

Trisomy 16 is frequently found confined to the placenta (confined placental mosaicism (CPM)), with a structurally normal fetus. In some cases of trisomy 16, the fetus has uniparental disomy for chromosome 16 (UPD16) which is associated with intrauterine growth restriction (IUGR) and fetal anomalies. We report a case of apparent confined placental mosaicism for trisomy 16, using standard cytogenetic techniques, but with multiple fetal abnormalities including congenital diaphragmatic hernia in which there was no evidence of UPD in the disomic tissues examined. Subsequent examination of fetal tissues using fluorescent in situ hybridization (FISH) demonstrated low levels of mosaicism for trisomy 16 in all the tissues examined. The use of FISH permits identification of mosaicism which conventional techniques may not identify.

Abnormalities, Multiple↗
PubMed2000

Distribution of the interleukin-8 receptors, CXCR1 and CXCR2, in inflamed gut tissue.

There is increasing evidence to suggest that the potent neutrophil chemoattractant interleukin-8 (IL-8) has an important role in the pathogenesis of inflammatory bowel disease. IL-8 mediates its actions via two cell surface receptors, CXCR1 and CXCR2. This paper describes the distribution of these IL-8 receptors in the normal gastrointestinal tract and how this is modified in ulcerative colitis (UC). Paraffin-embedded colonic resection specimens were stained with monoclonal antibodies directed against CXCR1 and CXCR2 in ten cases of total UC, 16 cases of appendicitis, and 11 histologically normal sections. A semiquantitative scale of 0-4 was used to assess the proportion and intensity of positively stained cells within certain defined areas of tissue. A comparative assessment was made of the distribution of various cell populations. Dual immunostaining was used to confirm the phenotype of positively staining cells. In the histologically normal colon, the antibody against CXCR1 stained a subpopulation of macrophages deep to the epithelium and germinal centre lymphocytes. A similar pattern of staining was seen in acute appendicitis, with in addition some positively stained neutrophil polymorphs. In UC, there was up-regulation of CXCR1, with a striking increase in positively stained macrophages throughout the mucosa and of B and T lymphocytes outside the germinal centre areas. There was also intense up-regulation of CXCR1 expression by the luminal epithelium, reflected in the epithelial staining score (mean+/-SE=1.8+/-0.44 for UC cases, vs. 0.23+/-0.16 for controls and 0.25+/-0.14 for acute appendicitis). CXCR2 was only expressed on a small population of lamina propria mononuclear cells and crypt epithelial cells, with no significant differences observed between the groups. These results suggest that IL-8 may, through CXCR1, have a role beyond neutrophil recruitment in mediating the immune response in UC and that this is not merely a consequence of the acute inflammation seen in UC.

Acute Disease↗
PubMed2000

Measurement of oilfield chemical residues in produced water discharges and marine sediments.

During oil production, significant quantities of water are produced with the crude oil which, following treatment on the platform, are discharged to the marine environment. This produced water contains residues of oilfield chemicals added by the platform operators to the topside processing equipment to aid oil-water separation and mitigate operational problems. The levels of oilfield chemicals entering the marine environment via this route were investigated using electrospray ionisation tandem mass spectrometry (ESI-MS/MS) and wet chemical analysis techniques. The generic nature of different chemical types was shown by ESI-MS/MS. Studies of the partitioning behaviour of corrosion inhibitors and demulsifiers between the oil and water phases of the produced fluids suggested corrosion inhibitors partitioned primarily into the aqueous phase and demulsifiers into the oil phase. This was reflected in levels observed in produced water although, in the case of a corrosion inhibitor, lower than expected concentrations were measured. Scale inhibitors were discharged with the produced water at their dosing concentrations. Marine sediments in the proximity of two North Sea oil platforms contained low levels of benzalkonium quaternary ammonium salts (0.74-10.84 ng/g), typical corrosion inhibitor chemicals.

Electron Spin Resonance Spectroscopy↗
PubMed2000

Impaired vasoconstriction in pregnancy-induced hypertension assessed using doppler fluximetry.

OBJECTIVE: To determine whether there is a difference in peripheral vascular reactivity between normal women and those with pregnancy-induced hypertension. METHODS: Capillary blood flow (flux) was recorded in the skin over the ankle in 26 pregnant women with pregnancy-induced hypertension at term. Twelve of these women had proteinuria, and 14 were nonproteinuric. Leg lowering was used to activate the venoarteriolar reflex, and the resultant change in flux, expressed as a percentage change from the baseline, was used as an index of vascular reactivity. The results were compared with those of a control group comprising 23 matched normotensive women. The study was repeated on all of the women after delivery. RESULTS: Women with hypertension showed a median (range) increase in flux of +24.4% (-15.5% to +151.1%), significantly different from controls: -39.3% (-80.9% to -4.3%, P <.001). This difference persisted regardless of the presence or absence of proteinuria. Responses in women with pregnancy-induced hypertension were significantly different after delivery (median -60.7%; range -158.5% to -19.5%, P <.001) when compared with predelivery responses. Similar changes as a result of delivery were seen in women with proteinuric (medians +25.9% and -57. 9%, P <.002) and nonproteinuric (medians +7.8% and -62.8%, P <.001) hypertension but not in controls. Postdelivery responses in women with hypertension were no different from those of controls. CONCLUSION: Women with pregnancy-induced hypertension have abnormal cutaneous vascular reactivity that returns to normal after delivery.

Adult↗
PubMed2000

Peroxisome distribution along the crypt-villus axis of the guinea pig small intestine.

Peroxisomes and peroxisomal enzyme expression were investigated biochemically and morphometrically in guinea pig intestinal epithelial cells at different stages of their migration along the crypt-villus axis. Epithelial cells were sequentially isolated along the axis and the specific activities of the peroxisomal enzymes catalase and acyl-CoA oxidase were found to be significantly higher in differentiated and mature cells situated at the villus tip and stem than in the crypt. Conversely, 1-alk-1'enyl, 2-acyl phospholipid (plasmalogen) concentration in the crypt and middle villus was significantly higher than in villus tip cells. Assay of alkyl DHAP synthase and fatty acyl CoA reductase (enzymes responsible for the production of plasmalogen precursors) showed no correlating activity gradient with plasmalogen concentration. Morphometric analysis revealed that peroxisomes were present even in the most immature stem cells, however, their number and volume and surface densities increased as the epithelial cell developed as did the proportion of elongated and vermiform peroxisomes to spherical structures. Senescent cells at the tip of the villus, however, showed a dramatic decrease in number of peroxisomes per cell possibly due to cellular degradation. We conclude that the peroxisomal compartment of the guinea pig small intestinal epithelial cell develops as a function of cell development possibly reflecting adaptation to maximise its metabolic capacity.

Animals↗
PubMed2000

Examination of trisomy 13, 18 and 21 foetal tissues at different gestational ages using FISH.

In man high levels of aneuploidy are seen in spontaneous abortions. Very few autosomal trisomies survive to birth, the three most common being those for chromosome 13, 18 and 21 giving rise to the syndromes named Patau, Edwards and Down respectively. Since the majority of these spontaneously abort, what makes the survivors different from the aborters? Could it be that they have tissue specific mosaicism with the additional normal cell line supporting survival? In this study fluorescence in situ hybridisation was used as a convenient way to detect trisomy in interphase cells. To study the level of mosaicism across gestation, different tissues from 21 trisomic foetuses were analysed using probes for chromosome 13, 18, 21, X and Y. Two trisomy 18 foetuses exhibited mosaicism. Two others, one trisomy 13 and one trisomy 18 had mosaic placentas. There was no clear association between the limited mosaicism seen and severity of the phenotype. We conclude that at least for this sample set, tissue-specific mosaicism was not likely to be responsible for potential survival to birth.

Adult↗