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Biomedical subjects

K Clayton

Publications and source records attributed to K Clayton.

15 recordsLinked to original sources
PubMed2002

A study of amsalog (CI-921) administered orally on a 5-day schedule, with bioavailability and pharmacokinetically guided dose escalation.

PURPOSE: Amsalog is a derivative of 9-aminoacridine. Phase I studies using intravenous (i.v.) amsalog have shown the dose-limiting toxicity (DLT) to be phlebitis and myelosuppression. Phase II studies using a variety of schedules have shown evidence of activity in patients with large-cell lung, breast, and head and neck cancers. Preclinical studies demonstrated that amsalog is active orally: a clinical study of the oral bioavailability of amsalog was therefore performed. METHODS: A group of 20 patients with refractory malignancies were treated. There were two phases of the study: a pharmacokinetic comparison of i.v. against oral amsalog, followed by a pharmacokinetically guided oral dose escalation study. In the first phase of the study, 11 patients were treated. Amsalog 50 mg/m2 was administered i.v., and 50 mg/m2 and 200 mg/m2 orally. In the second phase of the study, 9 patients were treated in three cohorts of three. On day 1 of a 5-day schedule, amsalog was administered i.v. at the maximum tolerated dose (MTD) of 200 mg/m2. Subsequent doses were given orally, starting at a dose of 200 mg/m2 per day, with intrapatient dose escalation of up to 100% for the second cycle. Doses were escalated further in subsequent cohorts, based on oral bioavailability and toxicity. RESULTS: Oral bioavailability of 50 mg/m2 amsalog was 34%. In the dose escalation phase, DLT was neutropenia; other toxicities included malaise and nausea. The MTD was 1600 mg/m2 per day for 5 days. The plasma AUC using 1600 mg/m2 by the oral route was higher than that achieved using 200 mg/m2 by the i.v. route. CONCLUSION: Amsalog can be tolerated orally on a 5-day schedule at doses up to 1600 mg/m2. The recommended dose for further evaluation is 800 mg/m2 daily for 5 days, repeated three weekly.

Administration, Oral↗
PubMed2001

Modulations in gene expression and mapping of genes associated with cyst nematode infection of soybean.

Infection of the soybean root by the soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) induces a well-documented, yet poorly understood, response by the host plant. The plant response, involving the differentiation of a feeding structure, or "syncytium," facilitates the feeding and reproduction of the nematode to the detriment of the host. We used a genetic system involving a single dominant soybean gene conferring susceptibility to an inbred nematode strain, VL1, to characterize the nematode-host interaction in susceptible line PI 89008. The restriction fragment length polymorphism marker pB053, shown to map to a major SCN resistance locus, cosegregates with resistance among F2 progeny from the PI 89008 x PI 88287 cross. Cytological examination of the infection process confirmed that syncytium development in this genetic system is similar to that reported by others who used noninbred nematode lines. Our study of infected root tissue in the susceptible line PI 89008 revealed a number of genes enhanced in expression. Among these are catalase, cyclin, elongation factor 1alpha, beta-1,3-endoglucanase, hydroxy-methylglutaryl coenzyme A reductase, heat shock protein 70, late embryonic abundant protein 14, and formylglycinamidine ribonucleotide synthase, all of which we have genetically positioned on the public linkage map of soybean. Formylglycinamidine ribonucleotide synthase was found to be tightly linked with a major quantitative trait locus for SCN resistance. Our observations are consistent with the hypothesis proposed by others that feeding site development involves the dramatic modulation of gene expression relative to surrounding root cells.

Animals↗
PubMed1998

Pulmonary nodule detection: low-dose versus conventional CT.

PURPOSE: To quantitate the effectiveness of low-dose computed tomography (CT) in the identification of pulmonary nodules while controlling for anatomic nodule characteristics and to establish what factors lead to reduced diagnostic sensitivity at low-dose CT. MATERIALS AND METHODS: Each of six participating radiologist independently rated 200 image panels by using a four-point confidence scale. Conventional images were obtained at 200 mAs; low-dose images were obtained at 20 mAs. To fully control their characteristics, nodules were simulated with a given diameter, shape, and section thickness while preserving the resolution, noise level, and reconstruction artifacts of the original images. Panels were matched so that nodules on low-dose and conventional images had equivalent sizes, locations, and relationships to blood vessels. RESULTS: Among 864 positive panels, 259 (60%) of 432 low-dose panels and 272 (63%) of 432 conventional panels were correctly interpreted (P = .259). Lowering the x-ray dose significantly reduced the detectability of peripheral nodules (P = .019) and nodules separated from blood vessels (P = .044). Surprisingly, 3-mm nodules were detected with approximately equal sensitivity (P = .181) at conventional and low-dose CT. The specificity of low-dose images was 88% (148 of 168 panels) versus 91% (153 of 168 panels) for conventional images (P = .372). CONCLUSION: Low-dose CT is acceptable for pulmonary nodule identification, making it suitable for primary screening. These results confirm the strong effect of size, location, and angiocentricity on the sensitivity of nodule detection with conventional CT.

Computer Simulation↗
PubMed1997

The relationship between overnight GH levels and insulin concentrations in adolescents with insulin-dependent diabetes mellitus (IDDM) and the impact of recombinant human insulin-like growth factor I (rhIGF-I).

OBJECTIVE: We examined the relationship between GH concentrations and free insulin concentrations, used as an index of insulin sensitivity, before and after recombinant human insulin-like growth factor I (RhIGF-I) administration in adolescents with insulin-dependent diabetes mellitus (IDDM). DESIGN AND PATIENTS: Growth hormone concentrations were assessed by a peak detection programme (Pulsar) on a control night (2000 h-0800 h) and a night when rhIGF-I administered in a subcutaneous dose of 40 micrograms/kg at 1800 h to 16 adolescent subjects. Stable euglycaemia was maintained by a continuous intravenous insulin infusion and changes in free insulin levels on the two nights were compared with growth hormone data. RESULTS: Mean overnight GH concentrations (2000 h-0800 h) on the control night were positively related to glycated haemoglobin (Hba1) concentrations (r = 0.63; P < 0.01) and were reduced following rhIGF-I administration (24.9 +/- 3.6 mU/I on the control night versus 17.4 +/- 2.2 mU/I after administration, P = 0.01). The mean GH pulse amplitude on the control night was related to the change in GH levels after rhIGF-I (rs = -0.66, P < 0.001). Multiple regression analysis revealed that mean GH pulse amplitude was the only determinant of free insulin concentrations (0500 h-0700 h on both study nights (P < 0.01). The percentage change in mean growth hormone pulse amplitude between the two nights was related to the percentage reduction in free insulin concentrations (r = 0.53, P = 0.03). CONCLUSIONS: Growth hormone pulse amplitude is related to early morning insulin sensitivity in adolescents with IDDM on control nights and after rhIGF-I administration. The reduction in insulin levels following rhIGF-I may be linked to the change in GH pulse amplitude and not just to direct insulin-like actions. Individuals with the higher GH (and thus HbA1 levels) were most sensitive to the GH-suppressive effects of rhIGF-I.

Adolescent↗
PubMed1997

Intensive care of patients with HIV infection: utilization, critical illnesses, and outcomes. Pulmonary Complications of HIV Infection Study Group.

To examine intensive care unit (ICU) admission rates and diagnoses of patients with HIV infection, and to determine the outcomes of different critical illnesses, we analyzed data derived from the 63 patients who were admitted to an ICU from among the 1,130 adults with HIV infection who did not have AIDS at the time of enrollment in a multicenter prospective study. Patients were admitted and treated according to the judgment of their physicians. During 4,298 patient-years of follow-up for the entire cohort, there were 1,320 hospital admissions, of which 68 (5%) included admission to an ICU. Twenty-five (40%) of the patients admitted to the ICU died during that admission. Twenty-four patients (38%) were admitted with a principal diagnosis of lung disease; 11 had Pneumocystis carinii pneumonia (PCP), one of whom was coinfected with Aspergillus fumigatus and Legionella pneumophilia, and six of them (55%) died. Four had bacterial pneumonia, two had pulmonary edema caused by renal failure, and one each had pulmonary tuberculosis, pulmonary Kaposi's sarcoma, pneumothorax, adult respiratory distress syndrome, severe pulmonary fibrosis, cytomegalovirus pneumonitis, and metastatic adenocarcinoma to the lungs. Eleven of these 14 patients (79%) died. Thirty-nine patients had 44 admissions for nonpulmonary diagnoses, including gastrointestinal disorders (14 admissions), cardiovascular disorders (nine), sepsis syndrome (six), neurologic disorders (four), monitoring and ICU nursing care during or after a procedure (four), metabolic disorders (three), trauma (two), drug overdose (one), and unknown reasons (one). Nine (23%) of these patients died. Twenty-eight patients underwent mechanical ventilation, and 16 (57%) died. Seven (25%) had PCP (five died), seven had other primary pulmonary diseases (six died), and 14 were placed on mechanical ventilation for nonpulmonary disorders (five died). Survival did not correlate with CD4 count determined within 6 mo of admission to the ICU. In conclusion, the range of indications for critical care in patients with HIV infection is diverse. PCP accounted for only 16% of the ICU admissions, and mechanical ventilation for PCP and other pulmonary disorders was associated with a high mortality rate. In contrast, mechanical ventilation for nonpulmonary disorders, and admission to the ICU for nonpulmonary diagnoses was associated with a more favorable outcome.

Adult↗
PubMed1995

The effects of repeated daily recombinant human insulin-like growth factor I administration in adolescents with type 1 diabetes.

Reduced insulin-like growth factor bioactivity has been linked to poor metabolic control and growth hormone hypersecretion in adolescents with Type 1 diabetes. The safety and efficacy of recombinant human insulin-like growth factor I administered subcutaneously in a dose of 40 micrograms kg-1 for 28 days was studied in a group of 6 adolescent male subjects with Type 1 diabetes (aged 13.6-19.4 years, puberty stage 3-5). After a 4-week run-in period (week -4 day 0) recombinant human insulin-like growth factor I was administered for 4 weeks (day 0 to week +4) before a run-out of a further 4 weeks duration (week +4 to +8). HbA1c levels were measured throughout the study and overnight profiles were undertaken to study levels of insulin-like growth factor 1, insulin-like growth factor binding protein-3, and growth hormone concentrations (week -1, day 0, and week +4). The injections were well tolerated and hypoglycaemia was not problematic at any stage of the study. Recombinant insulin-like growth factor I administration appeared to lead to a sustained increase in insulin-like growth factor I levels (week -1; 198 +/- 16 ng ml-1, week +4; 422 +/- 18 ng ml-1, mean +/- SEM; p = 0.03). Insulin-like growth factor binding protein-3 concentrations (n = 6) increased in 5 subjects (week -1; 4.5 +/- 0.3 micrograms ml-1, week +4; 5.1 +/- 0.4 micrograms ml-1) and mean overnight growth hormone decreased (week -1; 14.0 +/- 3.1 mUI-1, week +4; 7.6 +/- 1.7 mUI-1) during the period of study but these differences were not statistically significant. HbA1c levels fell significantly at the time of rhIGF-I administration (day 0; 10.4 +/- 1.9% vs week +4; 9.4 +/- 1.9%; p = 0.03) despite a reduction in subcutaneous isophane insulin dose from 0.50 +/- 0.02 U kg-1 to 0.41 +/- 0.02 U kg-1 (p = 0.03). There was no significant change in biochemical and haematological indices, glomerular filtration rate or urinary albumin excretion. The restoration of IGF-I levels in adolescents with Type 1 diabetes may have a beneficial impact on glycaemic control.

Aged↗
PubMed1994

The effects of recombinant human insulin-like growth factor-I (IGF-I) administration on the levels of IGF-I, IGF-II and IGF-binding proteins in adolescents with insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) during puberty is associated with a reduction in circulating concentrations of insulin-like growth factor-I (IGF-I) and low IGF bioactivity. Altered levels of the IGF-binding proteins (IGFBPs), including low IGFBP-3 and elevated IGFBP-1, have also been described. These abnormalities have been linked to poor growth and deteriorating blood glucose control. We have therefore examined the effects of recombinant human IGF-I (rhIGF-I) administration on the levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3 and IGF bioactivity in a group of 9 late-pubertal adolescents with IDDM. This was a double-blind placebo controlled study with each individual admitted on two occasions when either rhIGF-I (40 micrograms/kg) or placebo was administered by subcutaneous injection in the thigh at 1800 h. Blood samples were then taken for the subsequent 22 h. The half-life of administered rhIGF-I (12.1-22.2 h) was similar to that previously described in normal subjects. There was a small increase in IGFBP-3 concentrations overnight following rhIGF-I administration when compared to placebo, whereas the levels of IGF-II decreased. Under strict euglycaemic conditions, the relationship between insulin and IGFBP-I did not appear to be affected by rhIGF-I administration although the levels of IGFBP-1 tended to be higher overnight. IGF bioactivity was low during the placebo study, and although within the normal adult range following administration of IGF-I, was still relatively low for adolescents in late puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

The perception of natural contour.

The observation that natural curves and surfaces are often fractal suggests that people may be sensitive to their statistical properties. The perceptual protocols that underlie discrimination between fractals and between other types of random contour and fractals are examined. Discrimination algorithms that have precisely the same sensitivities as human observers are constructed. These algorithms do not recognize the integrated scale hierarchy intrinsic to fractal form and operate by imposing a metatheory of structure that is based on a signal-noise distinction. The success of the algorithms implies that (a) self-affinity in random fractals is not perceptually recovered and (b) people have a natural disposition to view contour in terms of signal and noise. The authors propose that this disposition be understood as a principle of perceptual organization.

Female↗
PubMed1991

Extradural vein puncture--an avoidable complication.

Accidental cannulation of an extradural vein is a troublesome and potentially serious complication of extradural catheter insertion. This study was conducted to assess the influence of posture, catheter size and the injection of saline before catheter insertion, on its occurrence. Eight different techniques were studied based on combinations of these three factors. There was no difference in incidence with respect to posture. The use of 18-gauge catheters, after injection of 10 ml of 0.9% saline, resulted in a significant (p less than 0.01) reduction in the incidence of extradural vein cannulation. This technique is recommended in obstetric patients as a means of avoiding accidental intravenous injection of local analgesic.

Adolescent↗
PubMedDate not supplied

Spinal bracing in the institutionalized person with scoliosis.

Twenty institutionalized children with scoliosis were treated with a spinal bracing program for an average of two years. The Boston brace with or without superstructure was employed. These children generally had neuromuscular disease and were often functional sitters only. Seizure disorders were common. Fifteen thoracolumbar curves were improved from a prebracing mean curvature of 4.25 degrees to a postbracing mean curvature of 31 degrees. The three lumbar curves improved from 39 degrees to 30 degrees. On patient was termed a failure. The program is considered to be of definite benefit.

Adolescent↗