Search PubMed⌕ Search

Biomedical subjects

G Graham

Publications and source records attributed to G Graham.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effect of recombinant GM-CSF on the metabolism of cytosine arabinoside in normal and leukemic human bone marrow cells.

Human recombinant GM-CSF (rGM-CSF) is under investigation as a growth-protective agent for normal hematopoietic elements in phase I trials of myelosuppressive chemotherapy and in bone marrow transplantation. We determined the effect of rGM-CSF on the metabolism of high dose Ara-C in bone marrow mononuclear cells (BMMCs) from healthy volunteers and patients with ANLL. Cells were incubated with rGM-CSF alone, Ara-C alone, or a combination of the two drugs. Treatment with rGM-CSF alone yielded approximately a twofold increment in intracellular dCTP pools in normal BMMCs but not in leukemic blasts. Exposure to rGM-CSF in conjunction with Ara-C corrected Ara-C-mediated declines in dCTP levels and decreased cytosine arabinoside triphosphate (Ara-CTP) accumulation in normal BMMCs but not in their leukemic counterparts. Furthermore, when exposure to Ara-C was preceded by treatment with rGM-CSF for 18 hr, an even greater reduction in the Ara-CTP/dCTP pool ratio was observed in normal versus leukemic elements; however, this did not significantly change Ara-C DNA incorporation in the two cell types. The differential effect of rGM-CSF on the phosphorylation of Ara-C in normal BMMCs versus leukemic blasts has potential implications for the use of a regimen consisting of rGM-CSF and high dose Ara-C in the treatment of ANLL with chemotherapy or autologous bone marrow transplantation.

Bone Marrow↗
PubMed1988

Psychologic testing in amputation rehabilitation.

Sixty adult patients had psychologic testing following successful below- or above-knee amputation surgery. All were considered to be prosthetic candidates based on the evaluation of an experienced multidisciplinary rehabilitation team. Objective psychologic testing revealed that six (10%) had severe deficits in cognitive ability, eight (13%) had covert psychiatric illness, and three (5%) had both. A vigorous attempt at prosthetic limb fitting and gait training was made in every patient in an inpatient rehabilitation unit. Of the 17 patients (28%) who were determined to be poor candidates for prosthetic limb fitting and gait training based on objective psychologic testing, only four (6%) were capable of even minimal use of the prosthesis, and none approached their preamputation level of ambulation. Psychologic testing may play an important role in determining the rehabilitation potential of the dysvascular amputee.

Adult↗
PubMed1987

The doctor, the rich, and the indigent.

This essay explores the major conflict between doing the best for indigents requiring health care and not unfairly imposing burdens on those who pay for that care through cost-shifting. The author argues that there is in fact no dilemma or conflict of duties presented here, but only because the doctor's concern with justice in bearing the burden of health care requires a system within which different levels of health care are available and in which indigent care is provided in a manner that minimizes the cost of providing that care.

Cost Allocation↗
PubMed1987

Effect of deoxycytidine on the metabolism and cytotoxicity of 5-aza-2'-deoxycytidine and arabinosyl 5-azacytosine in normal and leukemic human myeloid progenitor cells.

The effect of deoxycytidine (dCyd) on the inhibitory effects of two antileukemic nucleoside analogs, 5-aza-2'-deoxycytidine and ara-5-aza-Cyd, toward the clonogenic growth of normal human bone marrow progenitors (CFU-GM) and leukemic blast progenitors (L-CFU) was examined. Continuous exposure of cells to 10(-6)-10(-5) M 5-aza-deoxycytidine or 10(-5)-5 x 10(-5) M ara-5-aza-Cyd in conjunction with a 10- 100-fold excess of dCyd resulted in significantly greater restoration of CFU-GM growth than L-CFU colony formation at each dose relationship. Normal bone marrow mononuclear cells exposed to 10(-3) M dCyd for 4 hr (along with 5-aza-dCyd or ara-5-aza-Cyd) exhibited intracellular deoxycytidine triphosphate (dCTP) pools 20-fold higher than their leukemic counterparts. However, this finding was not associated with enhanced analog incorporation into leukemic cell DNA. These results suggest that high concentrations of dCyd preferentially protect normal versus leukemic progenitor cells from the inhibitory actions of 5-aza-dCyd and ara-5-aza-Cyd. They also raise the possibility that this in vitro selectivity may be related to enhanced expansion of dCTP pools in normal bone marrow elements and involves factors other than differential short-term analog incorporation into DNA.

Acute Disease↗
PubMed1987

Deoxycytidine preferentially protects normal versus leukemic myeloid progenitor cells from cytosine arabinoside-mediated cytotoxicity.

We examined the ability of high concentrations of the naturally occurring nucleoside deoxycytidine (dCyd) to reverse the cytotoxicity of high (eg, greater than or equal to 10(-5) mol/L) concentrations of 1-B-D arabinofuranosylcytosine (Ara-C) toward normal (CFU-GM) and leukemic myeloid progenitor cells (L-CFU). Leukemic myeloblasts from patients with acute nonlymphocytic leukemia (ANLL) and normal human bone marrow mononuclear cells were cultured in soft agar in the continuous presence of 10(-5) to 5 X 10(-5) mol/L of Ara-C together with dCyd (10(-4) to 5 X 10(-3) mol/L). Administration of 10(-5) mol/L of Ara-C alone eradicated colony formation in all samples tested. Coadministration of 10(-3) mol/L of dCyd restored 72.2% of control colony formation for CFU-GM, but only 10.9% for L-CFU. When higher concentrations of Ara-C (eg, 5 X 10(-5) mol/L) were administered, dCyd-mediated protection toward CFU-GM decreased, but remained significantly greater than that observed for L-CFU. Incubation with 10(-3) mol/L of dCyd reduced the 4-hour intracellular accumulation of the triphosphate derivative of Ara-C (Ara-CTP) in both normal and leukemic cells by greater than 98%; under identical conditions, a significant expansion of the intracellular of the triphosphate derivative of dCyd (dCTP) pools was observed in normal bone marrow mononuclear cells but not in leukemic blasts. This finding was associated with a greater reduction in Ara-C DNA incorporation in normal elements. These in vitro studies suggest that dCyd may preferentially protect normal v leukemic myeloid progenitor cells from the lethal actions of high-dose Ara-C.

Antineoplastic Agents↗
PubMed1986

Deoxycytidine stimulates the in vitro growth of normal CFU-GM and reverses the negative regulatory effects of acidic isoferritin and prostaglandin E1.

We have examined the effect of supraphysiologic concentrations of the naturally occurring nucleoside deoxycytidine (dCyd) on the in vitro growth of normal (CFU-GM) and leukemic (L-CFU) myeloid progenitor cells. Bone marrow samples obtained from 34 consecutive patients undergoing routine diagnostic bone marrow aspirations for nonmalignant hematologic disorders exhibited nearly a twofold increment in CFU-GM when continuously cultured in the presence of 10(-4) mol/L dCyd. Higher dCyd concentrations were associated with a smaller degree of enhancement of colony formation. In contrast, the growth of leukemic blast progenitors obtained from patients with acute nonlymphocytic leukemia were not enhanced by any of the dCyd concentrations tested. Coadministration of 10(-3) mol/L tetrahydrouridine (THU), a cytidine deaminase inhibitor, failed to alter the relative inability of dCyd to enhance L-CFU colony growth. The stimulatory effect of dCyd on normal CFU-GM was not mediated by the adherent mononuclear cell population of the marrow, nor was it restricted to the subpopulation of CFU-GM in S phase at the time of initial exposure. Moreover, treatment of normal bone marrow cells with dCyd at concentrations ranging from 10(-6) to 5 X 10(-3) mol/L for 24 hours had only a minor effect on the fraction of CFU-GM in S phase. Coadministration of 10(-4) mol/L dCyd was able to reverse the inhibitory effects of several putative regulators of normal myelopoiesis, including leukemia inhibitory activity (LIA), acidic isoferritins (AIF), and prostaglandin E1 (PGE1). Leukemic myeloblasts exposed to 10(-4) mol/L dCyd exhibited substantial expansion of intracellular pools of dCyd triphosphate (dCTP), demonstrating that inability to metabolize dCyd could not be solely responsible for the absence of growth potentiation in these cells. These studies suggest that supraphysiologic concentrations of dCyd may confer a selective in vitro growth advantage upon normal v leukemic myeloid progenitor cells, and may free the former from the inhibitory effects of several potential negative regulators of myelopoiesis.

Alprostadil↗
PubMed1986

A quality control system and its application to clinical chemistry.

A quality control system is presented that involves the Quality Control Log for documenting data, decisions, and corrective actions. It emphasizes the use of the Calibration Work Record, cusum, and comparison of means to monitor acute and chronic drift and method bias. It introduces clinically useful limits criteria for efficient and cost-effective quality control.

Calibration↗
PubMed1985

Stereoselective disposition of ibuprofen enantiomers in man.

This study has examined the stereoselective disposition of the enantiomers of ibuprofen in four healthy male subjects following separate administration of racemic ibuprofen (800 mg) and of each enantiomer (400 mg). A mean of 63 +/- 6% of an administered dose of R(-) ibuprofen was stereospecifically inverted to the S(+) enantiomer. There were no measurable inversion of the S(+) to R(-) ibuprofen. The kinetics of the individual enantiomers were altered by concurrent administration of the respective optical antipode. It is likely that this change reflects an interaction between the enantiomers at plasma protein binding sites. It was found that formation of ester glucuronide conjugates stereoselectively favoured the S(+) enantiomer. The data have demonstrated that the pharmacokinetics of ibuprofen and other alpha-methylarylacetic acids cannot be interpreted adequately without studying the pharmacokinetics of the individual enantiomers.

Adult↗
PubMed1985

Simultaneous occurrence of idiopathic lipemic tears and massive seborrhea.

A 42-year-old man had idiopathic lipemic tears and massive seborrhea. Recent investigations have shown that cholesterol and other lipids occasionally found in tears are produced by meibomian rather than lacrimal glands. The finding in this patient of hypersecretion by both sebaceous glands and meibomian glands, a sebaceous gland variant, suggests that a common mechanism may regulate secretory control of both of these glands.

Adult↗
PubMed1985

Gallium-67/technetium-99m methylene diphosphonate ratio imaging: early rabbit osteomyelitis and fracture.

Simultaneous digital acquisition of [67Ga] and [99mTc]MDP images, and subsequent division of the first by the second to produce a parametric ratio image (G/T), is employed to characterize the relative localization of the two radiopharmaceuticals in early rabbit tibia Staphloccocus aureus osteomyelitis and fracture repair. Images obtained during the first 48 hr of each condition show preferential 67Ga accumulation probably reflecting an initial inflammatory response while G/T images at 5-7 days show predominance of the bone-seeking scan agent, which may indicate that the dominant process is osteoblastic repair.

Animals↗
PubMed1985

Quality control log with CUSUM and clinically useful limits criteria.

We describe a quality control (QC) log including its advantages over the more commonly used Levey-Jennings and Shewart graphic charts. It represents a practical system of analytic quality control for quantitative assays in clinical chemistry. It utilizes cumulative sum (CUSUM) techniques and comparison of means to monitor acute and chronic analytic drift, respectively. Clinically useful limits (CUL) criteria for QC decisions are used. An algorithm to facilitate the description of, training for, and use of, the QC log system is provided.

Chemistry, Clinical↗
PubMed1984

Disposition of and clinical response to salicylates in patients with rheumatoid disease.

The disposition of salicylic acid (SA) and its metabolites and the clinical response to long-term aspirin treatment at varying doses were assessed in patients with rheumatoid disease. Steady-state kinetics of SA (total and unbound), salicyluric acid (SUA), gentisic acid (GA), and clinical status were estimated weekly in 10 patients with rheumatoid arthritis. Eight received a soluble aspirin form and two received an enteric-coated form. The starting dose of aspirin in each patient was 1.8 gm (soluble) or 1.95 gm (enteric-coated) daily. Weekly increments in dose were made until a satisfactory clinical outcome was achieved. The final aspirin dose range was 3.6 to 8.1 gm daily, which resulted in mean steady-state plasma SA concentrations (CpSA) from 56 to 375 mg/l. Since the mean total CpSA increased approximately proportionately over the dose range, there was little change in total SA clearance. By contrast, increasing aspirin dosage resulted in decreased clearance and disproportionate increases in unbound SA (CpuSA). The maximum velocity of conversion of SA to SUA (Vm) increased significantly, from 57.3 +/- 11.7 mg/hr at an aspirin dose of 1.8 gm/day to 71.4 +/- 19.4 mg/hr at the next highest dose (2.7 to 3.6 gm/day), with no further change with increasing dosage. Km ranged from 0.4 to 1.2 mg/l for CpuSA and from 5.5 to 17.2 for total CpSA. Renal clearance of SUA (ClSUA) ranged from 124 to 893 ml/min and correlated with creatinine clearance. ClGA ranged from 23 to 164 ml/min, and ClSA ranged from 0.1 to 17.1 ml/min; neither correlated with creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

The outlook for children after cardiac surgery: ventricular septal defects.

The indications for and results of surgical closure of ventricular septal defect (VSD), uncomplicated by other congenital cardiac defects, depend on the size of the VSD and its haemodynamic consequences. In infants the timing of surgical closure is determined largely by the persistence of symptoms of congestive cardiac failure unresponsive to maximal medical treatment. There is a high incidence of spontaneous closure of VSD with age, especially in defects of small size. Accompanying aortic regurgitation is a serious complication. Progress in surgical technique (e.g. deep hypothermia, cardioplegia, identification of the conduction tissue) has substantially decreased the hospital mortality of surgical closure and the incidence of late deaths. In selected series the hospital mortality has been reduced to as low as 1-2% in patients over one year of age. Unless there is intractable cardiac failure (rarely observed beyond infancy), surgical closure can be delayed: pulmonary vascular obstructive disease develops only very exceptionally below the age of two years. Late complications include re-opening of the patch repair, arrhythmias and conduction disorders. The prognosis of post-operative left axis deviation plus right bundle branch block (left anterior hemiblock) is good in the absence of serious arrhythmias. Late deaths are rare. Operation in early childhood prevents the occurrence or persistence of abnormal right ventricular function. Exercise tolerance is normal in the absence of complications in practically all patients, who can therefore lead a normal life in all respects. There is, however, still slight doubt to what extent surgical closure is truly "curative" rather than "corrective".

Age Factors↗
PubMed1982

High-frequency low-dose multiple-drug chemotherapy in advanced metastatic breast cancer.

A small group of patients (22) with metastatic breast cancer, most of whom had advanced visceral disease, have been treated since 1973 with low-dose, multiple-drug chemotherapy: vinblastine, 0.05 mg/kg, I.V.; cyclophosphamide, 6 mg/kg P.O.; 5-fluorouracil, 500 mg. P.O., and methotrexate, 0.3 mg/kg P.O. The schedule includes the use of one drug on each of four days every week. The drugs were taken in the sequence listed on alternate days, except that dosages of methotrexate and vinblastine were consecutive. The remission rate was 68% (15/22). The median duration of remission was 30 months. The median survival time of responding patients exceeds 40 months. Of the 15 responding patients, six (40%) remain alive with a mean survival time of more than 46 months. The regimen causes minimal toxicity and has been willingly accepted by patients for as long a period as 54 months. A therapeutic advantage appears to have been achieved by this high-frequency, low-dose schedule.

Adult↗
PubMed1982

Is diagnostic curettage harmful in women with unexplained infertility?

Diagnostic curettage as part of the investigation of the woman with unexplained infertility has not been considered a hazardous procedure. Two similar groups with unexplained primary infertility were examined laparoscopically: 53 patients had undergone diagnostic curettage as part of the investigation; 142 had not. None had an antecedent history suggestive of pelvic inflammatory disease. The incidence of laparoscopically detected chronic pelvic inflammatory changes in both groups was compared and was found to be 50.9 and 13.4% respectively (P less than 0.001). It was concluded that diagnostic curettage may be more hazardous in women with unexplained infertility than was believed previously.

Dilatation and Curettage↗
PubMed1981

Enteric-coated pelletized aspirin. Gastrointestinal blood loss and bioavailability.

Eleven patients suffering from arthritis received, in a randomized cross-over study, anti-inflammatory doses of two aspirin formulations: Enpryn, capsules containing enteric-coated pellets; Rhusal, an enteric-coated tablet. No significant difference was found between the two formulations with respect to gastrointestinal microbleeding, plasma salicylate levels and urinary recovery of salicylate. Bioavailability studies carried out on 10 healthy male volunteers demonstrated that absorption from the enteric-coated pellet capsules was sustained and complete.

Aspirin↗
PubMed1981

Factors influencing survival after balloon atrial septostomy for complete transposition of great arteries.

Despite balloon atrial septostomy within the first days of life, some patients with complete transposition of the great arteries die before reaching elective definitive surgery in the second six months of life. To discover why, we analysed the fate of 144 patients who had balloon atrial septostomy after 1966, using a modified logrank survival test with multivariate capability. Patients were withdrawn "alive" on reaching definitive surgery. The following largely independent factors were associated with a statistically significant excess mortality: pulmonary hypertension, the presence and size of a ventricular septal defect of persistent ductus arteriosus, relative anaemia, absence of left ventricular outflow tract obstruction, low arterial oxygen saturation, aortic stenosis and coarctation, and balloon atrial septostomy between 1 week and 1 month of life. Those of the above factors which can be determined at balloon atrial septostomy or at routine cardiac catheterisation at 3 months of age were then introduced into discriminant function analysis on survival to 6 months. Hence the probability of any individual patient dying in the first six months was calculated, allowing for these factors. This prediction was correct in 76 per cent of the patients studied. By offering earlier definitive correction to patients thus identified as being at high risk of premature death, it should prove possible to reduce overall mortality in transposition of the great arteries.

Age Factors↗