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Biomedical subjects

P Palmer

Publications and source records attributed to P Palmer.

At least 19 recordsLinked to original sources
PubMed1995

An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy.

The CD34 antigen is expressed by committed and uncommitted hematopoietic progenitor cells and is increasingly used to assess stem cell content of peripheral blood progenitor cell (PBPC) collections. Quantitative CD34 expression in PBPC collections has been suggested to correlate with engraftment kinetics of PBPCs infused after myeloablative therapy. We analyzed the engraftment kinetics as a function of CD34 content in 692 patients treated with high-dose chemotherapy (HDC). Patients had PBPCs collected after cyclophosphamide based mobilization chemotherapy with or without recombinant human granulocyte colony-stimulating factor (rhG-CSF) until > or = 2.5 x 10(6) CD34+ cells/kg were harvested. Measurement of the CD34 content of PBPC collections was performed daily by a central reference laboratory using a single technique of CD34 analysis. Forty-five patients required a second mobilization procedure to achieve > or = 2.5 x 10(6) CD34+ cells/kg and 15 patients with less than 2.5 x 10(6) CD34+ cells/kg available for infusion received HDC. A median of 9.94 x 10(6) CD34+ cells/kg (range, 0.5 to 112.6 x 10(6) CD34+ cells/kg) contained in the PBPC collections was subsequently infused into patients after the administration of HDC. Engraftment was rapid with patients requiring a median of 9 days (range, 5 to 38 days) to achieve a neutrophil count of 0.5 x 10(9)/L and a median of 9 days (range, 4 to 53+ days) to achieve a platelet count of > or = 20 x 10(9)/L. A clear dose-response relationship was evident between the number of CD34+ cells per kilogram infused between the number of CD34+ cells per kilogram infused and neutrophil and platelet engraftment kinetics. Factors potentially influencing the engraftment kinetics of neutrophil and platelet recovery were examined using a Cox regression model. The single most powerful mediator of both platelet (P = .0001) and neutrophil (P = .0001) recovery was the CD34 content of the PBPC product. Administration of a post-PBPC infusion myeloid growth factor was also highly correlated with neutrophil recovery (P = .0001). Patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin had more rapid platelet recovery than patients receiving other regimens (P = .006), and patients requiring 2 mobilization procedures versus 1 mobilization procedure to achieve > or = 2.5 x 10(6) CD34+ cells/kg experienced slower platelet recovery (P = .005). Although a minimal threshold CD34 dose could not be defined, > or = 5.0 x 10(6) CD34+ cells/kg appears to be optimal for ensuring rapid neutrophil and platelet recovery.

Adolescent↗
PubMed1995

An MRI study of brain size in autism.

OBJECTIVE: This study was undertaken to obtain detailed measurements of the volume of the brain, using magnetic resonance imaging (MRI), in a carefully selected group of autistic subjects and comparison subjects. METHOD: Twenty-two male autistic subjects and 20 male volunteer comparison subjects were examined with detailed (1.5-mm slices) MRI throughout the entire brain. Total brain, total brain tissue, and total lateral ventricle volumes were measured by using manual tracing and automated techniques. RESULTS: After height and performance IQ were controlled, autistic subjects had significantly greater total brain, total tissue, and total lateral ventricle volumes than comparison subjects. CONCLUSIONS: These findings suggest that male autistic subjects have enlarged brains and that enlargement is a result of both greater brain tissue volume and greater lateral ventricle volume.

Adolescent↗
PubMed1994

Objective system for interviewer performance evaluation for use in epidemiologic studies.

In this paper, the authors present an objective system to evaluate interviewer performance for use in epidemiologic studies. With this quality control system, all study interviews are audio-taped, and a random sample of interviews are coded according to interviewer behaviors, such as whether the interviewer asked the questions exactly as written and used the probes appropriately. With the use of data obtained from a large case-control study of colon cancer, the authors observed that 94.2% of all questions were asked in the same manner by all interviewers and that 89.5% of all probing behaviors were appropriate. They show that questions that required additional interviewer behaviors were more likely to result in variation in response that can be attributed to the interviewer. These findings have implications for study design and interpretation of study results. From simulations, the authors have estimated the impact of uncorrected interviewer variability on study power and ability to detect disease associations. Uncorrected interviewer variability could decrease study power from 84% to 56%. From simulations, the authors observed that odds ratios could be biased downward from 1.8 to 1.3. These findings illustrate the importance of using a continuous quality control program in epidemiologic research.

Epidemiologic Methods↗
PubMed1993

Evaluation of the right atrial venous oxygen saturation as a physiologic monitor in a neonatal model.

Pulmonary artery (PA) mixed venous saturation (SvO2) has become a crucial monitor in the adult intensive care unit, but is not used in neonates because of the difficulty in PA catheterization. We evaluated the possibility of utilizing the right atrial venous oxygen saturation (RAvO2), which is easily accessed in the neonate, as a monitor of the effects of mechanical ventilation and intravascular volume in an animal model selected to be the size of the human neonate. A continuous RAvO2 monitoring catheter was placed into the right atrium of 16 normal rabbits (2.2 to 4.1 kg). Oxygen delivery was manipulated by alterations in peak inspiratory pressure (PIP) (n = 6), positive end-expiratory pressure (PEEP) (n = 6), or by progressive hypovolemia (n = 4). RAvO2 decreased with onset of mechanical ventilation alone from 69% +/- 6% to 61% +/- 5% (P < .01). As the PIP was increased from 12 to 21 cm H2O, the RAvO2 progressively decreased from 59% +/- 4% to 49% +/- 6% (P < .05). As the PEEP was increased from 3 to 9 cm H2O, the RAvO2 progressively decreased from 64% +/- 5% to 33% +/- 16% (P < .01). RAvO2 approached baseline after return to continuous positive airway pressure (CPAP) of 3 cm H2O. Progressive phlebotomy to a total of 10 mL/kg resulted in a decrease in RAvO2 from 70% +/- 6% to 27% +/- 5% (P < .001). Volume resuscitation resulted in an increase in RAvO2 to near baseline. Peripheral arterial oxygen saturation remained at a constant 100% throughout each protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Responses of children to booster immunization with their primary conjugate Haemophilus influenzae type B vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid.

Children primed with one of four conjugate Haemophilus influenzae type b vaccines received booster immunization with their primary vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid. The latter vaccine produced postbooster antibody levels that equaled or exceeded those produced by boosting with the original vaccine, and thus may be used as a booster irrespective of the original vaccine.

Antibodies↗
PubMed1993

A phase-III study of recombinant interleukin 2 and 5-fluorouracil chemotherapy in patients with metastatic colorectal cancer.

Sixteen patients with metastatic colorectal cancer have been treated with a regimen involving an 120 h continuous infusion of rIL-2, 18 x 10(6) iu m-2 day followed by three injections of 5FU 600 mg m-2 at weekly intervals. Entry criteria included no previous chemotherapy, ambulatory performance status, and a measurable lesion. In most cases side effects were easily manageable and only one patient required transfer to an intensive care unit with the capillary leak syndrome. In three patients persistent hypotension was found to be unrelated to treatment with rIL-2, being caused respectively by a line infection, pulmonary embolus, and bowel perforation. This last proved a fatal complication. Five patients (33%; [95% confidence limits, 11.8%-61.6%]) achieved a partial response, and two non-responders later achieved a partial response when treated with weekly 5FU. This regimen is currently being evaluated in a phase-III randomised controlled trial.

Abdominal Neoplasms↗
PubMed1993

The impact of interleukin-2 on survival in renal cancer: a multivariate analysis.

The purpose of this analysis was to compare the survival of patients with advanced renal carcinoma treated with intravenous recombinant interleukin-2 to the survival of matched patients taken from the large and well characterised database of the Eastern Cooperative Oncology Group (ECOG). Recombinant interleukin-2 (rIL-2) given by continuous intravenous infusion was used to treat 387 patients with advanced adenocarcinoma of the kidney in five multi-centre studies and 327 of these patients fulfilled the study eligibility criteria and were evaluable for response, toxicity and survival. The survival of patients treated with rIL-2 was compared in a multi-variate survival analysis taking account of all identified prognostic factors to 390 control patients receiving chemotherapy derived from the database. Thirteen patients treated with rIL-2 achieved a complete remission of their disease and 32 a partial remission giving an overall response rate of 14%. Remissions were durable with a median duration of 357 days for partial remissions and a median duration in excess of 926 days for complete remissions. Most patients experienced fever or mild to moderate hypotension and other toxicities are described. However, only 11 patients required admission to intensive care and in only five cases was this judged to be due to treatment toxicity. There were three deaths judged to be probably due to treatment toxicity. rIL-2 treatment was associated with significantly prolonged survival compared to the ECOG control patients. Patients with good prognostic features appeared to have a greater survival benefit from rIL-2 than those with poor prognostic features. This analysis provides the first evidence that rIL-2 prolongs survival in patients with advanced renal cancer but cannot provide proof which should be sought in randomised prospective trials drawing on the hypotheses generated herein.

Adult↗
PubMed1992

Comparative trial in infants of four conjugate Haemophilus influenzae type b vaccines.

We performed a double-blind, randomized trial to compare the immunogenicity and reactogenicity of four conjugate Haemophilus influenzae type b vaccines given to infants 2, 4, and 6 months of age. Adverse reactions attributable to the vaccines were few and minor. The rates of systemic reactions did not differ among the various vaccines and were similar to those seen among children receiving conventional diphtheria-tetanus-pertussis vaccine. However, the four conjugate H. influenzae type b vaccines differed markedly in ability to stimulate antibody production. Mean antibody levels after three injections of polyribosylribitol phosphate conjugated with mutant diphtheria protein (PRP-CRM) or polyribosylribitol phosphate conjugated with tetanus toxoid (PRP-T) were 3.08 micrograms/ml and 3.64 micrograms/ml, respectively, significantly higher than those after the use of polyribosylribitol phosphate conjugated with outer-membrane protein of Neisseria meningitidis (PRP-OMP) (1.14 micrograms/ml) or polyribosylribitol phosphate conjugated with diphtheria toxoid (PRP-D) (0.28 microgram/ml). Only PRP-OMP produced a clinically pertinent elevation in antibody level after two injections (0.84 microgram/ml); the third injection of PRP-OMP produced a modest but statistically significant further elevation in mean antibody level (1.14 micrograms/ml). Only 29% of infants receiving PRP-D had antibody levels of 1 micrograms/ml, compared with 55%, 75%, and 83% of those receiving PRP-OMP, PRP-CRM, and PRP-T, respectively. We conclude that all four vaccines are safe and that all but PRP-D appear appropriate for use in a primary immunization series during infancy. The unique serologic response to PRP-OMP offers both advantages and disadvantages in comparison with PRP-CRM and PRP-T.

Antibody Formation↗
PubMed1991

Effect of prolonged subcutaneous administration of interleukin-2 on the circadian rhythms of cortisol and beta-endorphin in advanced small cell lung cancer patients.

Interleukin-2 has been shown to stimulate cortisol secretion in man. Owing to its immunosuppressive properties, an increase in cortisol levels during interleukin-2 cancer immunotherapy could potentially counteract induced activation of the antitumor immune response. Few data are available about cortisol secretion secondary to prolonged interleukin-2 administration. To investigate the problem, we evaluated cortisol circadian rhythms in 7 consecutive metastatic small cell lung cancer patients who received interleukin-2 subcutaneously for 4 weeks (daily dose: 6 x 10(6) x IU/m2). Venous blood samples were drawn at 8.00 a.m., 4.00 p.m. and 12.00 p.m., before interleukin-2, and after each week until the end of the cycle. Beta-endorphin levels were also measured on the same samples. Four patients were evaluated during a second interleukin-2 cycle. Mean cortisol levels increased during interleukin-2 therapy, but were significantly higher than those seen in basal conditions after the first week of treatment. Moreover, cortisol peaks observed during the second cycle of therapy were not significantly different from those seen during the first cycle. Mean beta-endorphin levels increased in response to interleukin-2 administration, but the increase did not reach statistical significance. The early cortisol rise progressively decreased as treatment continued. This suggests that the interleukin-2-induced cortisol rise has no relevant clinical importance in antagonizing the activation of an effective antitumor immune response during cancer immunotherapy with interleukin-2.

Carcinoma, Small Cell↗
PubMed1991

Local activation of immune response in bladder cancer patients treated with intraarterial infusion of recombinant interleukin-2.

Tumor regression induced in cancer patients by i.v. infusion of interleukin-2 (IL-2) is often accompanied by severe side effects. To investigate whether local administration would affect immune response without the side effects, two 5-day cycles of continuous intraarterial [internal iliac artery] infusion of recombinant interleukin-2 (rIL-2) were performed in 12 patients with transitional cell carcinoma (tumor stage 1, node stage 0, metastasis stage 0, and grade 1-2) of the bladder. Four groups of 3 patients were treated at each of 4 escalating doses of rIL-2 (18 x 10(3), 18 x 10(4), 18 x 10(5), and 18 x 10(6) IU/m2/day) throughout the course of the two IL-2 cycles. This treatment was effective in inducing a marked intratumor inflammatory response, consisting mainly of T-lymphocytes and macrophages. A remarkable dose-dependent increase in the levels of soluble CD25 was observed in the urine of all patients, which was associated constantly with an enhanced number of intratumor CD25+ cells. Intratumor macrophages were often immunoreactive for interleukin-1 and/or tumor necrosis factor, suggesting an activated status. Increased levels of soluble CD25 and CD25+ lymphocytes were observed in peripheral blood only at the two highest doses of rIL-2, while increased percentages of circulating HLA-DR+ and CD71+ lymphoid cells and enhancement of CD3+/CD16+ T-lymphocytes were found at lower doses. Peripheral blood eosinophils were augmented in almost all patients but were rarely increased in situ. We provide evidence that continuous intraarterial infusion of rIL-2 activates host immune response, acting preferentially at the tissue level.

Antigens, CD↗
PubMed1989

Immunization after invasive Haemophilus influenzae type b disease. Serologic response to a conjugate vaccine.

Fifteen children with previous invasive Haemophilus influenzae type b disease were immunized with a Hemophilus-diphtheria toxin mutant protein conjugate vaccine. Serologic responses were compared with those of 31 newly immunized children without previous invasive H influenzae type b disease. Mean levels of antibody to polyribosylribitol phosphate among study children younger than 18 months were 0.086 mg/L before immunization, 0.737 mg/L after first immunization, and 4.453 mg/L after second immunization. In contrast, the comparable mean polyribosylribitol phosphate antibody levels among control children younger than 18 months were 0.107, 3.580, and 63.502 mg/L. A similar pattern of results was found among children aged 18 months or older. Although children with previous invasive H influenzae type b disease do not respond as vigorously to conjugate vaccine as do previously healthy controls, the response is sufficient to justify routine immunization of such children.

Age Factors↗