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Biomedical subjects

M Graham

Publications and source records attributed to M Graham.

At least 37 records · Page 2Linked to original sources
PubMed1990

A phase I toxicity, pharmacology, and dosimetry trial of monoclonal antibody OKB7 in patients with non-Hodgkin's lymphoma: effects of tumor burden and antigen expression.

Eighteen patients with relapsed non-Hodgkin's lymphoma (NHL) were infused with escalating doses of monoclonal antibody (mAb) OKB7, trace-labeled with iodine-131 (131I), in order to study toxicity, pharmacology, antibody localization, and dosimetry of radioiodine. OKB7 is a noncytotoxic mouse immunoglobulin G2b (IgG2b) mAb reactive with B cells and most B-cell NHL. Three patients each were treated at six dose levels ranging from 0.1 mg to 40 mg. All patients had radionuclide imaging and counting daily, had serial blood sampling to study pharmacokinetics, human antimouse antibody (HAMA), and circulating antigen, and had a biopsy of accessible lymphoma to determine delivery of isotope to tumors and assess the effect of tumor antigen expression on mAb delivery. Bone marrow biopsies were also done in the majority of patients. There was no toxicity. Serum clearance showed a median early phase half-life of 1.9 hours and a later phase half-life of 21.7 hours. Median total body clearance half-life was 22 hours. Pharmacokinetics were not dose-related. HAMA was detected in five patients. Circulating blocking antigen was detected in the serum of four patients, but at levels that were of pharmacologic consequence only in one. Biopsied tumor tissue from five patients did not express OKB7 antigen. No significant uptake of antibody was seen in these tumor sites. Mean total uptake of isotope into lymphoma measured in biopsies correlated linearly over the 400-fold increase in injected mAb dose. However, the percent of injected dose found per gram of tumor was unrelated to dose, but correlated inversely with tumor burden. In two patients with minimal tumor burden, 1.0 mg and 5.0 mg doses of OKB7 resulted in tumor to body radioisotope dose ratios of 22 and 7, which would theoretically permit tolerable delivery of 4,400 and 1,400 rads to these tumors, respectively, if OKB7 were conjugated with higher doses of 131I.

Adult↗
PubMed1990

Phencyclidine and violent deaths in St. Louis, Missouri: a survey of medical examiners' cases from 1977 through 1986.

A survey of 104 deaths involving phencyclidine (PCP) occurring from 1981 through 1986 in metropolitan St. Louis, Missouri, is presented. Four black males (22-33 yr) died from fatal PCP intoxication. PCP was detected in an additional 100 deaths: 81 homicides, 13 suicides, and 6 accidental deaths. Seventy-five of these deaths were homicides of Black males (mean age 27 years) typically dying from gunshot wounds, 64 cases. In 50% of deaths where PCP was detected, other drugs were co-administered: ethanol (35%) and cocaine (20%) being the most common mixtures. A dramatic continuous increase in PCP abuse from 1984 through 1986 was demonstrated by drug abuse indicator data: treatment admissions, emergency room episodes, police exhibits, and driving under the influence of PCP arrests. Increased abuse of PCP in St. Louis has been associated with increased medical emergencies and violence against persons.

Accidents↗
PubMed1990

Magnetic resonance imaging demonstrates that electric stimulation of cerebellar fastigial nucleus reduces cerebral infarction in rats.

We sought to determine whether high spatial resolution magnetic resonance imaging is useful for noninvasive quantitation of the ischemic infarct produced by occlusion of the middle cerebral artery and for detection of reduced infarct volume elicited by electric stimulation of the cerebellar fastigial nucleus. Male rats of the spontaneously hypertensive strain were anesthetized, the middle cerebral artery was occluded, and the fastigial nucleus was stimulated for 1 hour. Twenty-four hours later, rats were reanesthetized and T1- and T2-weighted images were obtained. Rats were killed and the volume and distribution of the lesion was established by histopathology. Magnetic resonance imaging estimates of the lesion volume were 271 +/- 41.0 mm3 (middle cerebral artery, n = 5) and 148 +/- 8.4 mm3 (middle cerebral artery + fastigial nucleus stimulation, n = 6; 45% reduction, p less than 0.05). Histopathological analysis revealed a lesion of 229.8 +/- 15.4 mm3 involving somatosensory cortex, lateral caudate putamen, and lateral hippocampus. Fastigial nucleus stimulation resulted in a 36% reduction in infarct volume to 146.0 +/- 10.3 mm3. The retrieved zone was largely in the cortex dorsal and ventral to the lesion and mostly posterior to the lesion. The estimates of lesion volume by magnetic resonance imaging and histopathology did not differ and were highly correlated (r = 0.90; p less than 0.001). This study confirms our previous finding that fastigial nucleus stimulation reduces the volume of a focal ischemic infarct and demonstrates that magnetic resonance imaging not only accurately estimates the volume of the lesion but also can detect changes as small as 50-100 mm3.

Animals↗
PubMed1989

Hypercholesterolaemia and a silent MI.

Results of investigations in extraordinary patients should be dealt with cautiously; it is often prudent to repeat tests. Though the aims of treatment in such cases are often the same, differences in approach to the problem are illuminating.

Adult↗
PubMed1989

Circulating lymphocytes, neutrophils and immune complexes in pigs after feeding.

There are reports in the literature claiming that pigs experience a lymphopenia after feeding. This is not observed in other species. We set out to investigate this phenomenon because of the unusual route of lymphocyte recirculation in pigs. for it suggested that this might be a specific response to dietary antigens. We were unable to confirm this phenomenon. A lymphopenia was observed in both test and control groups as a non-specific response to restraint and blood sampling. In contrast, feeding was associated with a significant neutrophilia (mean 58%, P less than 0.002). There were no increases in circulating IgA, IgG or IgM immune complexes after feeding but IgG immune complexes remained at a higher level than in the control group.

Animals↗
PubMed1989

The use of lymphoscintigraphy in treatment planning of primary breast cancer.

A technique is described for the use of lymphoscintigraphy in treatment planning of primary breast patients. During simulation of the treatment fields, the positions of the internal mammary nodes are projected back toward the source onto the patient skin surface and are marked by radio-opaque markers for visualization on films. Exact solutions for the coordinates of these surface projection points are derived. Approximate solutions are also given which are independent of the isocenter location and primarily dependent on the treatment field gantry angle. If a typical couch angle and field size are assumed, the projection points can be calculated for various gantry angles prior to simulation. Generally, a decision can then be made beforehand whether it would be better to use deep tangents or a separate field to treat the internal mammary nodes. During simulation, the surface projection points serve as visual and fluoroscopic guides to field design and optimization. A method is also presented for projecting the internal mammary node positions onto a single transverse patient contour for conventional 2-dimensional treatment planning. By accurately showing the projected location of the node with respect to the field edge, adequate treatment margin can be assured.

Breast Neoplasms↗
PubMed1989

Leukemic retinopathy. Relationship between fundus lesions and hematologic parameters at diagnosis.

The authors examined 117 consecutive patients with acute leukemia within a few days of diagnosis. Sixty-six patients had acute nonlymphocytic leukemia, and 51 had acute lymphocytic leukemia. Forty-two percent of the patients had abnormal ocular findings related to leukemia. The authors found an association between the presence of intraretinal hemorrhages and thrombocytopenia for all patients. In addition, patients with acute lymphocytic leukemia and intraretinal hemorrhages had lower hematocrit levels than did those without such hemorrhage. The presence of anemia was related to the findings of white-centered hemorrhages in patients with acute nonlymphocytic leukemia. The presence of cotton-wool spots was not associated with hematologic parameters. Intraretinal hemorrhages, white-centered hemorrhages, and cotton-wool spots were all found more frequently in adults than in children.

Adolescent↗
PubMed1989

Intermediate-dose intravenous methotrexate and mercaptopurine therapy for non-T, non-B acute lymphocytic leukemia of childhood: a Pediatric Oncology Group study.

Methotrexate (MTX) and mercaptopurine (MP) are the mainstays of continuation therapy for acute lymphocytic leukemia (ALL). These drugs are stored in tissues as active metabolites. Relapse in ALL might reflect failure to achieve adequate intracellular drug levels. Assured (parenteral) delivery of higher doses of MTX and MP should maximize tissue levels of these drugs by overcoming individual variations in absorption, metabolism, clearance, and compliance. Fifty-nine children with ALL at lower risk of relapse received 12 intensive MTX/MP courses immediately after 4 weeks of standard vincristine, prednisone, and asparaginase induction. Each 2-week intensive course included: MTX, 200 mg/m2 intravenous (IV) push then 800 mg/m2 IV over 24 hours on day 1; MP, 200 mg/m2 IV push then 800 mg/m2 IV over 8 hours on day 2; MTX, 20 mg/m2 intramuscularly on day 8; and MP, 50 mg/m2 orally daily on days 8 to 14. After the 6 months of intensive therapy, continuation therapy was weekly MTX/MP (as on days 8 to 14) for 1 or 2 years. Age-based MTX was given intrathecally (IT) for CNS prophylaxis. All patients entered remission. Three patients relapsed: bone marrow (at 24 and 37 months), and bone marrow and CNS (at 34 months). There were no isolated CNS relapses or deaths in remission. Event-free survival at 4 years is 94% (SE, 7%) by Kaplan-Meier analysis. Toxicities (infection, mucositis) occurred in less than 10% of intensive MTX/MP courses. However, a child with Down's syndrome withdrew after three courses because of recurrent severe mucositis. Further studies of this regimen are in progress.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Trace element deficiencies in inflammatory bowel disease.

Since the institution of successful parenteral nutrition, much has been learned about malnutrition and the effects and complications of nutritional therapy. A variety of patient groups suffer from malnutrition, and clinicians accept the fact that an extremely high incidence of hospitalized medical and surgical patients are malnourished. Perhaps the group we most frequently see suffering from malnutrition are patients with inflammatory bowel disease (IBD). This is especially true in Crohn's disease, in which a variety of nutritional disturbances have been described.

Humans↗
PubMed1988

RglB facilitated cloning of highly methylated eukaryotic DNA: the human L1 transposon, plant DNA, and DNA methylated in vitro with human DNA methyltransferase.

In vitro methylation of Bluescribe plasmid DNA (pBS) with human placental DNA methyltransferase to 6% 5-methylcytosine (mC) reduced transformation efficiencies in rglB+ host strains C600 and DS410 by almost 2 orders of magnitude. By contrast, the rglB- derivative of DS410 showed no reduction in transformation efficiency with methylation while the rglB- derivative of C600 was partially tolerant to methylation. Further, we show that the 1.8 kilobase (kb) and 1.2 kb KpnI fragments derived from the human L1 repeat have respectively 18.3% and 2.3% mC in vivo. Using these hyper- and hypo-methylated genomic segments ligated into the pBS plasmid, transformants with the highly methylated 1.8 kb L1 insert were recovered at 17 to 40 fold higher frequency with the rglB- host strains than with the rglB+ hosts. In addition, recombinant phage (lambda 2001) containing inserts of plant genomic DNA with 26.7% mC (from Petunia hybrida) when plated on rglB- hosts gave titres up to 222 times higher than on the rglB+ strains.

Cell Line↗
PubMed1988

Ultrasound screening for clinically occult abdominal aortic aneurysm.

In a review of the records of 74 patients who had undergone repair of an abdominal aortic aneurysm at a community hospital between 1977 and 1983 we found that the aneurysm had been undiagnosed before rupture in 35%; these patients had an operative death rate of 50%, whereas elective repair carried a death rate of 4%. The characteristic patient was an obese man over the age of 55 years with hypertension, coronary artery disease, cerebrovascular disease or peripheral vascular disease. Ultrasound examination was performed in 45 patients with these characteristics, and six aneurysms were diagnosed. Either surgery or computed tomography confirmed the diagnosis. The rate of false-negative results was estimated by review of the charts of 100 men over the age of 55 years who had undergone abdominal ultrasonography for other indications: no undetected aneurysms were discovered over 3 years of follow-up. Routine screening in this high-risk group would improve the rate of diagnosis of this potentially fatal condition before rupture and offer the patient the lower mortality rate associated with elective surgery.

Aged↗
PubMed1988

Nevus cell aggregates in the placenta. A histochemical and electron microscopic study.

This is a report of the histochemical and ultrastructural analysis of nevus cell aggregates in the placenta from a neonate with a giant pigmented nevus. Although the distinction between aberrant migration of neural crest elements and blood-borne metastasis from the giant pigmented nevus is not readily resolved, the authors favor the former as an explanation of this unusual placental lesion.

Biopsy↗
PubMed1988

The evolution and outcome of cavitating periventricular leukomalacia in infancy. A study of 46 cases.

Forty six infants with the ultrasonic diagnosis of cavitating periventricular leukomalacia (CPVL) have been reviewed. Follow up examination results allow correlation between the ultrasound appearances and subsequent neurodevelopmental and neurological deficits. The highest incidence of this condition was found in infants at and below 27 weeks gestation, and occurred in 15% of very premature infants surviving 14 days or more. Cavities developed 15 days after the onset of periventricular echodensity (median time). Ventricular dilatation occurred in 24% of the infants who developed cavities. Follow up information was available in 27 infants and 18 of these (67%) had significant neurodevelopmental handicap. The location of echolucent cavities were described as involving anterior, middle or posterior cerebral zones or any combination of these. Cerebral palsy was closely related to the presence of cavities, but there was little association between cavities and developmental delay. Four factors were found to predict cerebral palsy: cavities within the occipital zone, the involvement of multiple regions of the brain, lesions greater than 1 cm in diameter and cavities associated with subcortical leukomalacia. Lesions confined to the anterior or middle zones were unlikely to be associated with significant handicap. The presence of cavities per se was not associated with a higher incidence of severe developmental delay.

Cerebral Palsy↗
PubMed1988

Non-Hodgkin's lymphomas.

The non-Hodgkin's lymphomas are a group of diseases for which substantial progress has been made in understanding tumor biology and effectiveness of treatment during the last few years. These advances may provide insight into the development of neoplasms because of recognized association of lymphomas with viral infections and immunodeficiency. The prognosis for patients with non-Hodgkin's lymphomas continues to improve. As a result, current studies on treatment of lymphomas in certain favorable stages have concentrated on reducing the intensity of therapy. For patients with advanced disease, further improvements in treatment are being sought.

Adolescent↗