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J Cox

Publications and source records attributed to J Cox.

At least 91 records · Page 5Linked to original sources
PubMed1998

DNA adducts of 2,3-epoxy-4-hydroxynonanal: detection of 7-(1', 2'-dihydroxyheptyl)-3H-imidazo[2,1-i]purine and 1,N6-ethenoadenine by gas chromatography/negative ion chemical ionization/mass spectrometry.

2,3-Epoxy-4-hydroxynonanal (EH) is a bifunctional aldehyde formed by epoxidation of trans-4-hydroxy-2-nonenal, a peroxidation product of omega-6 polyunsaturated fatty acids. EH is mutagenic and tumorigenic and capable of modifying DNA bases forming etheno adducts in vitro. Recent studies showed that etheno adducts are present in tissue DNA of humans and untreated rodents, suggesting a potential endogenous role of EH in their formation. A sensitive assay is needed so we can determine whether EH is involved in etheno adduct formation in vivo and study the biological significance of the etheno adducts in DNA. In this study, we developed a gas chromatography/negative ion chemical ionization/mass spectrometry assay for the analysis of 1, N6-ethenoadenine (epsilonAde) and 7-(1', 2'-dihydroxyheptyl)-3H-imidazo[2,1-i]purine (DHH-epsilonAde) in DNA; both are products from the reaction of adenine with EH. The assay entails the following sequence of steps: (1) addition of [15N5]epsilonAde and [15N5]DHH-epsilonAde to DNA as internal standards, (2) acid hydrolysis of DNA, (3) adduct enrichment by C18 solid phase extraction (SPE), (4) derivatization by pentafluorobenzylation (PFB), (5) separation of PFB-epsilonAde and PFB-DHH-epsilonAde on a Si SPE column, (6) acetonide (ACT) formation of PFB-DHH-epsilonAde, and (7) GC/MS analysis with selective ion monitoring (SIM). The limit of detection by on-column injection for PFB-epsilonAde monitoring of the (M - PFB)- ion at m/z 158 was 30 amol and for ACT-PFB-DHH-epsilonAde monitoring of the (M - PFB)- ion at m/z 328 was 0.4 fmol; the detection limits for the entire assay were 6.3 fmol for epsilonAde and 36 fmol for DHH-epsilonAde. In calf thymus DNA modified with EH at 37 degreesC for 50 h, both epsilonAde and DHH-epsilonAde were detected at high levels by this method, 4.5 +/- 0.7 and 90.8 +/- 8.7 adducts/10(3) adenine, respectively. These levels were also verified by HPLC fluorescence analysis, indicating that EH extensively reacts with adenine in DNA, forming etheno adducts. The high sensitivity of the assay suggests that it may be used in the analysis of ethenoadenine adducts in vivo.

Adenine↗
PubMed1998

Progression of diabetic nephropathy--is diurnal blood pressure rhythm as important as absolute blood pressure level?

BACKGROUND: Hypertensive non-diabetic patients who lack the normal nocturnal decline in blood pressure ('non-dippers') have an increased incidence of cardiovascular complications. Poor blood pressure control is known to exacerbate the decline in glomerular filtration rate in patients with diabetic nephropathy. METHODS: The aim of this study was to assess the contribution of abnormal blood pressure diurnal rhythm to the progression of diabetic nephropathy. We retrospectively studied 26 diabetic patients with hypertension, proteinuria and relentless progressive impairment of renal function due to diabetic nephropathy between 1990 and 1996. Patients underwent ambulatory blood pressure monitoring and were classified as either 'dippers' or 'non-dippers' according to their blood pressure diurnal rhythm. Dippers were patients whose mean sleeping blood pressure (both systolic and diastolic) was 10% less than blood pressure whilst awake. Weight, glycated haemoglobin, serum creatinine (micromol/l) and blood pressure (mmHg) were recorded on a 3-monthly basis. Twenty four hour urine protein excretion and creatinine clearance were recorded annually. The rate of decline of creatinine clearance was derived from serum creatinine estimation. RESULTS: In the 'dipper' group, the rate of decline of creatinine clearance was -2.9 ml/min/year and in those with abnormal blood pressure diurnal rhythm it was -7.9 ml/min/year (P<0.05). There was no significant difference in day-time mean blood pressures, glycated haemoglobin, age and numbers with insulin-dependent diabetes mellitus. CONCLUSION: We found that there was a profound effect of non-dipping upon the rate of decline of renal function in patients with diabetic nephropathy.

Adult↗
PubMed1998

Comparison of neutrophil and monocyte function by microbicidal cell-kill assay in patients with cancer receiving granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, or no cytokine after cytotoxic chemotherapy: a phase II trial.

Functional effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were prospectively measured by harvesting blood samples from 51 oncology patients (21 who were receiving no cytokines, 14 receiving rhGM-CSF, and 16 who were receiving rhG-CSF) just before cytotoxic chemotherapy (baseline) immediately before the last cytokine dose (pre), 2 hours after the last cytokine dose (post), and 48 hours after the pre period (follow-up). Neutrophils and monocytes were separated and functional effects were measured by comparing cell-kill percentages, as determined by a microbial cell-kill assay against Staphylococcus aureus and Candida albicans. Optimal cell concentrations (2 x 10(6) monocytes/ml; 4 x 10(6) neutrophils/ml) and effector-to-cell ratios (1:50) were initially determined with blood samples harvested from 23 healthy volunteers. Results in oncology patients indicated that rhGM-CSF improved monocyte-killing activity against S. aureus at follow-up, compared with controls (p = 0.0094) and compared with monocytes from rhG-CSF-treated patients at the post period (p = 0.014). Cell-killing percentage of the rhGM-CSF-treated patients was also enhanced against C. albicans during the post period, compared with controls (p = 0.011) and rhG-CSF-treated patients (p = 0.067). Neutrophil activity was not altered by either cytokine. In conclusion, monocyte-induced microbial killing was enhanced in oncology patients receiving rhGM-CSF after cytotoxic chemotherapy, compared with patients receiving rhG-CSF or no cytokines. No differences in neutrophil activity were observed between patients receiving either cytokine.

Candida albicans↗
PubMed1998

Conjugated estrogen reduces transfusion and coagulation factor requirements in orthotopic liver transplantation.

UNLABELLED: We conducted a prospective, randomized study to determine the efficacy of conjugated estrogen in reducing blood product transfusion during orthotopic liver transplantation (OLT). Patients undergoing OLT were included in the study. Only those having a reaction time of more than 30 mm or 15 min (19 -28 mm) on computed thromboelastography (CTEG) at the beginning of surgery were enrolled in the study. Patients were randomized to receive either conjugated estrogen (CE) or placebo. Every patient received a first dose of CE (100 mg i.v.) (20 mL) or placebo (20 mL of isotonic sodium chloride solution) at the beginning of the procedure and a second dose of CE (100 mg i.v.) or 20 mL of placebo (20 mL of isotonic sodium chloride solution) just after reperfusion of the new graft. The two groups were similar in age, weight, requirement for veno-veno bypass, time on veno-veno bypass, CTEG measurement, and preoperative hemoglobin and platelet values. Blood products were given in relation to hematocrit and coagulation (CTEG) variables, which were measured every hour during the surgery. The amount of transfused blood products did not differ in terms of units of cryoprecipitate, but the intraoperative requirements for red blood cells (6 +/- 3 vs 9 +/- 6 U; P = 0.05), platelets (12 +/- 8 U vs 18 +/- 10 U; P = 0.05) and fresh-frozen plasma (3 +/- 3 U vs 6 +/- 4 U; P = 0.001) was significantly less in the estrogen group than in the control group. We conclude that CE is associated with a significant decrease in use of fresh-frozen plasma, platelets, and red blood cells during OLT. IMPLICATIONS: In this study, we prospectively investigated whether i.v. conjugated estrogen could decrease blood product transfusion during orthotopic liver transplantation. Conjugated estrogen-treated patients received less fresh-frozen plasma, red blood cells, and platelets. In this population of patients, conjugated estrogen can be a useful addition in coagulation management during orthotopic liver transplantation.

Blood Coagulation Factors↗
PubMed1998

Effectiveness of conjugated estrogen in orthotopic liver transplantation.

BACKGROUND: A retrospective study was conducted at a university hospital to determine the efficacy of conjugated estrogen in reducing blood product transfusion during orthotopic liver transplantation. METHODS: The charts of patients who had orthotopic liver transplantation were retrospectively reviewed. Only those having a reaction time > 30 mm or 15 minutes (normal = 19 mm to 28 mm) on computerized thromboelastogram (CTEG) at the beginning of surgery were included. One group of patients received a first dose of conjugated estrogen (100 mg i.v.) at the beginning of the case and a second dose (100 mg i.v.) just after reperfusion of the new graft. The control group did not receive estrogen. The two groups were similar in age, weight, first TEG measurements, final intraoperative hemoglobin concentration and platelet count. Blood products were given in response to hematocrit and CTEG measurements, which were determined every hour during surgery. RESULTS: The two groups did not differ in units of cryoprecipitate and platelets administered, but the intraoperative requirements for red blood cells and fresh frozen plasma were significantly lower in the estrogen group than in the control group. CONCLUSIONS: Administration of conjugated estrogen is associated with a statistically significant decrease in use of red blood cells and fresh frozen plasma during orthotopic liver transplantation.

Adult↗
PubMed1998

Assessment of the effects of combination therapy with ciprofloxacin and fenbufen on the central nervous systems of healthy volunteers by quantitative electroencephalography.

The potential effects of concurrent administration of fenbufen and ciprofloxacin on central nervous system activity in healthy young subjects were investigated by electroencephalography (EEG). Visual analog scales (VAS) were used to assess subjective measures of concentration, vigilance, tension, and irritability. When ciprofloxacin was administered in combination with fenbufen, none of the EEG parameters or VAS ratings measured were significantly different from those measured when the drugs were administered alone.

Adult↗
PubMed1997

Desialylation of peripheral blood mononuclear cells promotes growth of HIV-1.

Activation of peripheral blood CD4+ helper T lymphocytes establishes a permissive state for growth of HIV-1. Activated T lymphocytes expressed increased sialidase (neuraminidase) activity and were hyposialylated. Treatment of freshly isolated peripheral blood mononuclear cells (PBMCs) with microbial neuraminidase (NANase) or phytohemagglutinin (PHA) prior to infection at low multiplicity with T cell line-adapted HIV-1IIIB resulted in production of large amounts of p24 antigen and reverse transcriptase. In contrast, neither viral component was detected in the medium of mock-treated cells infected at a similar multiplicity through 21 days in culture. The titer of a stock solution of HIV-1IIIB was 1.4 +/- 0.18 log10 greater in NANase-treated PBMCs than in mock-treated cells; the titer was similarly raised 1.5 to 1.76 +/- 0.18 log10 in PHA-treated cells. Growth of the primary isolate HIV-1(91/US/056) was also enhanced in NANase-treated PBMCs; the titer of a stock solution of HIV-1(91/US/056 was 1.0 +/- 0.16 log10 greater in NANase-treated PBMCs than in mock-treated cells 7 days after infection. No enhancement of viral growth in PBMCs was detected when NANase was heat-inactivated or specifically inhibited with 2,3-dehydro-2-desoxy-N-acetyl-neuraminic acid prior to use. Treatment of PBMCs with NANase did not alter the distribution of lymphocyte subsets nor change the density of CD4 antigen per cell after 7 days in culture. Whereas PHA treatment of PBMCs was mitogenic, pretreatment with NANase was not; the amount of [3H]thymidine incorporated into DNA and culture growth characteristics were similar for NANase- and mock-treated cells. Thus, desialylation of PBMCs promoted a permissive state for growth of HIV-1 without affecting the rate of DNA synthesis or relative number of target CD4+ cells.

Antigens, CD↗
PubMed1997

Predicting high-risk years for malaria in Colombia using parameters of El Niño Southern Oscillation.

The interannual variation in malaria cases in Colombia between 1960 and 1992 shows a close association with a periodic climatic phenomenon known as El Niño Southern Oscillation (ENSO). Compared with other years, malaria cases increased by 17.3% during a Niño year and by 35.1% in the post-Niño year. The annual total number of malaria cases is also strongly correlated (r = 0.62, P < 0.001) with sea surface temperature (SST) anomalies in the eastern equatorial Pacific, a principal parameter of ENSO. The strong relation between malaria and ENSO in Colombia can be used to predict high and low-risk years for malaria with sufficient time to mobilize resources to reduce the impact of epidemics. In view of the current El Niño conditions, we anticipate an increase in malaria cases in Colombia in 1998. Further studies to elucidate the mechanisms which underlie the association are required. As Colombia has a wide range of climatic conditions, regional studies relating climate and vector ecology to malaria incidence may further improve an ENSO-based early warning system. Predicting malaria risk associated with ENSO and related climate variables may also serve as a short-term analogue for predicting longer-term effects posed by global climate change.

Colombia↗
PubMed1997

An investigation of the effect of advancing uraemia, renal replacement therapy and renal transplantation on blood pressure diurnal variability.

BACKGROUND: Ambulatory blood pressure recordings have been shown to correlate better with target organ damage than have isolated clinic blood pressure readings. There have been some small studies demonstrating that abnormal blood pressure diurnal rhythm is common in uraemia and in patients on renal replacement therapy. Abnormal blood pressure diurnal rhythm itself may be a risk factor for accelerated target organ damage. METHODS: We retrospectively studied 480 ambulatory blood pressure recordings in 380 patients with essential hypertension, secondary hypertension, and on renal replacement therapy. We examined diurnal blood pressure rhythm in each group. RESULTS: Abnormal blood pressure diurnal rhythm (non-dipping) is significantly more prevalent in patients with underlying renal disease, even with normal excretory renal function (53%) than in age-, sex-, and race-matched controls with essential hypertension ((30%), P < 0.01). In patients with renal disease the prevalence of non-dipping rose with worsening renal function, reaching statistical significance once plasma creatinine was greater than 400 mumol/l. There was a direct correlation between plasma creatinine and percent decline in blood pressure at night for both systolic (r = 0.23) and diastolic (r = 0.24) blood pressure in patients with underlying renal disease and impaired excretory renal function. High prevalences of abnormal diurnal BP rhythm are seen in patients on haemodialysis (82%), peritoneal dialysis (78%), patients with plasma creatinine > 600 mumol/l (75%), and in renal transplant recipients (74%). CONCLUSIONS: Abnormal blood pressure diurnal rhythm ('non-dipping') is significantly more common in secondary than in primary hypertension, even with normal renal function. Abnormal blood pressure diurnal rhythm becomes increasingly common with advancing uraemia. Once the plasma creatinine is greater than 600 mumol/l the prevalence of non-dipping is the same as that seen with renal replacement therapy. This phenomenon is not modulated by successful renal transplantation.

Adult↗
PubMed1997

Irinotecan hydrochloride (CPT-11) resistance identified by K-ras mutation in patients with progressive colon cancer after treatment with 5-fluorouracil (5-FU).

OBJECTIVE: To determine the prognostic role of a K-ras mutation in tumor tissue of patients with refractory colon cancer who received irinotecan hydrochloride (CPT-11). METHODS: DNA was extracted from paraffin-stored tumor tissue of 35 patients with progressive colon cancer failing treatment with 5-fluorouracil who subsequently received CPT-11 (100 mg/m2 i.v. per week x 4 weeks with 2 weeks off per course). The first exon of the K-ras gene was amplified by polymerase chain reaction by using K-ras-specific primers followed by mutant enrichment sequencing. Survival differences of patients with a K-ras mutation were compared with those of patients with a normal K-ras status. RESULTS: A total of 21 patients had a normal K-ras sequence and 14 patients had a K-ras mutation [GAT, n = 7; TGT, n = 3; and GCT, AGT, GTT, GAC (codon 13), n = 1 each]. Median survival of patients with a normal ras sequence from time of treatment with CPT-11 was 332 days compared with 169 days for patients with a K-ras mutation (p = 0.0036). No differences in age, sex, cancer stage, surgical treatment, or chemotherapy treatment were observed. CONCLUSION: Determination of the presence of a K-ras mutation may predict survival in patients with progressive colon cancer after treatment with 5-fluorouracil who receive CPT-11.

Adenine↗
PubMed1997

Teenage pregnancy prevention programs.

Teen pregnancy is a multifaceted problem closely connected to economic, education, social, cultural, and political factors. Adolescents in the United States have the highest pregnancy rates in the Western world. Teen parenthood is associated with discontinued or delayed education, reduced employment opportunities, low wages, unstable marriages, and prolonged welfare dependency. Prevention of teen pregnancy has become an important national agenda. The purpose of this paper is to provide a review of teen pregnancy prevention programs and strategies and to highlight some of the most promising interventions.

Adolescent↗
PubMed1997

Primary parotid lymphoma: the effect of International Prognostic Index on outcome.

Since the reported survival and failure-free survival (FFS) of adults with primary parotid non-Hodgkin's lymphoma (NHL) is variable, we reviewed our experience of untreated adults with primary parotid NHL. Patients were eligible if they presented to the University of Texas M. D. Anderson Cancer Center Cancer between 1980 and 1995 with parotid enlargement and if the diagnosis of lymphoma was verified according the Working Formulation. Medical records were reviewed to determine Ann Arbor Stage (AAS), the International Prognostic Index (IPI) score, response to therapy, relapse, FFS, and survival. We identified 39 untreated adults with primary parotid NHL representing 1% of all lymphomas and 8.6% of all untreated parotid neoplasms. Three patients were excluded because of suboptimal therapy, leaving 36 patients eligible for outcome analysis. Of the 18 patients with low-grade NHL, two were treated with radiotherapy, eight with chemotherapy and radiotherapy, seven with chemotherapy only, and one with antibiotics. The complete remission (CR) rate was 94%, and with a median follow-up of 36 months for surviving patients the survival and failure-free survival (FFS) at 5 years were 94% and 78%, respectively. The 5-year FFS were not statistically different between patients with early (I or II) or advanced (III or IV) AAS (83% and 74%, respectively; p > 0.05) and favorable (0 or 1) or unfavorable (> 1) IPI scores (73% and 100%, respectively; p > 0.05). All 18 patients with intermediate-grade NHL were treated with doxorubicin-based chemotherapy which was followed by radiotherapy in six. The CR rate was 89%, and with a median follow-up of 51 months for surviving patients the survival and FFS at 10 years were 80% and 72%, respectively. In this group 10-year FFS was better in early than in advanced AAS (100% vs 0%, respectively; p = 0.01) and in favorable (0 or 1) than in unfavorable (> 1) IPI scores (86% vs 20%, respectively; p < 0.01). We conclude the the FFS of patients with low-grade NHL is 78% and not affected by AAS or IPI score. The FFS of patients with intermediate-grade NHL appears comparable with that of NHLs of other primary sites, being 86% for those with IPI < or = 1 and 20% for those with IPI 1. Patients with IPI > 1 should be entered on investigational protocols aiming to increase FFS.

Adult↗
PubMed1997

Rural general practice: a personal view of current key issues.

We know much less about health care needs and provision in rural areas than we do about urban areas, particularly the inner cities. Although rural areas are attractive, isolation and lack of accessible services create problems for residents, particularly for those without transport. Analysis of the problems is handicapped by the lack of generally acceptable definitions of the meaning of rurality and remoteness. Rural deprivation is not reflected in commonly used indices of deprivation and is often "hidden". There is a shortage of general practitioners and concern that the situation is deteriorating. What does this mean for the future? Should there be a 'rural track' in educational programmes for rural health workers? How can we harness telemedicine to improve communication between rural dwellers and primary health care, and between primary and secondary health care? Where will nurse practitioners fit into the picture? If centralised services (e.g. for accident and emergency) lead to higher quality of care, how can rural dwellers have equitable access? Some possible solutions are presented.

Cultural Deprivation↗