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Biomedical subjects

M E Miller

Publications and source records attributed to M E Miller.

At least 163 records · Page 9Linked to original sources

The ontogeny of pulmonary defenses: alveolar macrophage function in neonatal and juvenile rhesus monkeys.

Using the technique of bronchoalveolar lavage, we isolated alveolar macrophages (AM) from the lower respiratory tract of newborn (1-4 days of age), infant (6-10 days of age), juvenile (3-6 months of age), and adult rhesus monkeys. The AM thus obtained were assayed in vitro to determine their chemotactic, phagocytic, and candidicidal capabilities. The predominant (greater than or equal to 89%) cell type in bronchoalveolar lavage effluent in all ages was the AM. Chemotaxis, phagocytosis, and killing of Candida albicans were markedly impaired in neonatal AM as compared with those from infants, juveniles, and adults. AM chemotactic activity achieved normal adult values by 6 days of age. Phagocytosis, and to a lesser extent candidicidal activity, were significantly improved in 6-day-old animals, but adult levels were still not achieved even by 6 months of age.

Aging↗

Mandatory HMO enrollment in Medicaid: the issue of freedom of choice.

In areas where HMOs have enrolled a small proportion of the general population, physician participation is less in mandatory HMO programs for Medicaid beneficiaries than in fee-for-service Medicaid. But where HMOs have enrolled over one-quarter of the general population, participation rates are indistinguishable under the two systems. In those areas, mandatory enrollment restricts freedom of choice of provider. A plausible reason for this is that individual practice associations, which contract with large numbers of physicians with both fee-for-service and HMO patients, are becoming the lead form of HMO.

Civil Rights↗

Effect of fish oil concentrates on hemorheological and hemostatic aspects of diabetes mellitus: a preliminary study.

Fish oil concentrates (Max EPA) were given without other diet modification for eight weeks to five insulin-dependent diabetics and five healthy volunteers, in order to determine their effect on possible in vitro indices of thrombosis. Cholesterol, HDL, LDL, fasting blood sugar, hemoglobin A1c, platelet count, and the osmotic fragility of red blood cells were not significantly changed from baseline values after eight weeks of fish oil consumption. Serum triglyceride levels were lowered by the fish oil (diabetics 130 +/- 23 to 89 +/- 26 mg/dl: normals 107 +/- 16 to 57 +/- 5 mg/dl). Nine out of ten subjects required more arachidonic acid to aggregate their platelets, and six out of ten required more collagen. Whole blood viscosity at low shear rates was increased in diabetics before the fish oil ingestion, and was reduced both in normals and in diabetics after eight weeks of treatment. Before fish oil administration, the diabetics had higher levels of von Willebrand Factor (vWF) (208 +/- 31%) than did controls (117 +/- 26%). There was a statistically significant decrease of serum von Willebrand Factor both in diabetics (p less than 0.01) and in normals (p less than 0.05) after six weeks of treatment. Analysis of the multimeric composition of the vWF indicated that the vWF molecule was not altered. Addition of eicosapentaenoic acid (EPA) or crude fish oil to human umbilical cord endothelial cell cultures did not change vWF levels in the supernatant. Whether these changes in platelet aggregation, whole blood viscosity and vWF can actually be translated into an in vivo amelioration of the vascular complications in diabetes remains to be determined in a carefully controlled clinical trial.

Adult↗

Familial CHARGE syndrome: clinical report with autopsy findings.

We report on a patient with CHARGE syndrome, as manifested by a coloboma of the optic nerve head, congenital heart defect (ASD, VSD, and parachute mitral valve), choanal atresia, severe growth retardation, genital hypoplasia, abnormal ears, cleft lip and palate, and pectus carinatum. His chromosomes were normal. He died at 19 months. His mother was short and had hearing impairment, choanal atresia, and a coloboma. We suggest that this represents evidence for dominant transmission of this disorder in this family. Other familial cases from the literature are reviewed.

Abnormalities, Multiple↗

Quantitative microscopy: I. A computer-assisted approach to the study of polymorphonuclear leukocyte (PMN) chemotaxis.

A computer-assisted approach has been designed to analyze and quantitate polymorphonuclear leukocyte (PMN) chemotaxis. This approach involves a rapid, objective, and semiautomated (user-directed) image-analysis system that is video- and microscope-based. The entire system consists of a microvideo set-up that is put on line with a Digital DEC-LSI-11/73 microcomputer, interfaced with a Datacube analog-digital/digital-analog converter. Video signals of PMN movement are digitized by the system at a resolution of 240 pixels vertically by 320 pixels horizontally (at 256 gray levels) and stored in a 76,800-byte frame buffer. The digitized data are stored for later use or utilized immediately for image segmentation, image display, movement, and morphometric computations for each PMN in a maximum phase field (at 645 X high dry) of 50 PMNs at 10-second intervals. The digitized data are used for computation of cell perimeter, surface area, optical density, contour-ratio, position, speed, and direction of locomotion with the utilization of micro-image-analysis programs written in FORTRAN and MACRO assembly language, with the computer operating under RT-11/TSX+. The reliability, objectivity, and reproducibility of measurements made with this quantitative approach have been tested by comparing with manual-tracing measurements of PMN movement. A correlation factor of 0.99 has been obtained. However, the quantitative-microscopic approach is much faster, more objective, less tedious, and much easier to operate than the conventional manual-tracing method.

Chemotaxis, Leukocyte↗

Effects of low level radiation upon the hematopoietic stem cell: implications for leukemogenesis.

These studies have addressed firstly the effect of single small doses of x-rays upon murine hematopoietic stem cells to obtain a better estimate of the Dq. It is small, of the order of 20 rad. Secondly, a dose fractionation schedule that does not kill or perturb the kinetics of hemopoietic cell proliferation was sought in order to investigate the leukemogenic potential of low level radiation upon an unperturbed hemopoietic system. Doses used by others in past radiation leukemogenesis studies clearly perturb hemopoiesis and kill a detectable fraction of stem cells. The studies reported herein show that 1.25 rad every day decrease the CFU-S content of bone marrow by the time 80 rads are accumulated. Higher daily doses as used in published studies on radiation leukemogenesis produce greater effects. Studies on the effect of 0.5, 1.0, 2.0, and 3.0 rad 3 times per week are under way. Two rad 3 times per week produced a modest decrease in CFU-S content of bone marrow after an accumulation of 68 rad. With 3.0 rad 3 times per week an accumulation of 102 rad produced a significant decrease in CFU-S content of bone marrow. Dose fractionation at 0.5 and 1.0 rad 3 times per week has not produced a CFU-S depression after accumulation of 17 and 34 rad. Radiation leukemogenesis studies published to date have utilized single doses and chronic exposure schedules that probably have significantly perturbed the kinetics of hematopoietic stem cells. Whether radiation will produce leukemia in animal models with dose schedules that do not perturb kinetics of hematopoietic stem cells remains to be seen.

Animals↗

Cord serum bromide concentration: variation and lack of association with pregnancy outcome.

Excessive maternal bromide exposure during pregnancy from drugs and occupation have been reported to have adverse effects on the fetus and newborn, including central nervous system depression at birth and possible teratogenicity. To define further fetal bromide exposure during pregnancy, we determined the cord serum bromide concentration in 1267 newborn babies born in Rochester, New York, during the 6-month period from January 1, 1984 to June 30, 1984. There was a normal distribution of the cord serum bromide concentration values (mean +/- SD = 8.6 +/- 2.6 mg/L; range 3.1 to 28.5 mg/L). The highest concentration was still significantly below the minimal bromide concentration associated with toxic effects (720 mg/L). There was no association between the cord serum bromide concentration and indices of fetal health including Apgar scores, presence of congenital malformations, and neonatal disposition. No mothers were taking significant amounts of bromide-containing drugs during pregnancy. The second highest cord serum bromide concentration (21.4 mg/L) was in a woman who was an amateur photographer and developed her own film, which required her to use chemicals containing bromide. Our results indicate that excessive fetal bromide exposure is rare and probably occurs only in the setting of maternal use of bromide-containing drugs or occupational exposure during pregnancy.

Abnormalities, Drug-Induced↗

A computer-assisted image-analysis system for analyzing polymorphonuclear leukocyte chemotaxis in patients with diabetes mellitus.

A computer-assisted image-analysis system that precisely tracks the cell movements of up to 50 polymorphonuclear leukocytes (PMNLs) was developed and used to quantitatively measure cellular chemokinesis and chemotaxis in normal individuals and in diabetic patients with hyperglycemia. The PMNLs were tested in Zigmond chambers with or without a gradient of 10(-7) M n-formylmethionylleucylphenylalanine (f-Met-Leu-Phe). Cellular movement was recorded on videotape by using a videocamera mounted on the microscope. The videotapes were analyzed by computer programs to calculate the speed and direction of each PMNL at 10-sec intervals. Average rates of chemokinesis were 19.6 microns/min without and 25.3 microns/min with f-Met-Leu-Phe. McCutcheon indices, which measure chemotaxis, were 0.01 without and 0.48 with f-Met-Leu-Phe. Similar values were observed in diabetic patients after fasting (average glucose, 217 mg/100 ml) and 2 hr after glucose challenge (average glucose, 309 mg/100 ml). These values demonstrate that PMNLs from diabetic patients with hyperglycemia move at normal rates and respond appropriately to f-Met-Leu-Phe.

Adolescent↗

Chemotactic and phagocytic function of peripheral blood polymorphonuclear leucocytes in newborn foals.

Chemotactic and phagocytic responsiveness of peripheral blood polymorphonuclear leucocytes (PMNLs) from 11 foals were analysed immediately after birth (pre-colostral) and at different times after colostrum ingestion. The number of foal PMNLs per microscopic field that had migrated through the filter in chemotaxis and the number of yeast particles ingested per foal PMNL in phagocytosis were significantly lower when tested with foal plasma before colostrum ingestion (chemotaxis, 2.0 +/- 0.55 (s.e.m.); phagocytosis, 0.98 +/- 0.352) than in tests 4 or more days after colostrum ingestion (chemotaxis, 17.6 +/- 3.88; phagocytosis, 3.87 +/- 0.410; P less than or equal to 0.005). A similar functional deficiency was found in foal PMNLs tested with pre-colostral foal plasma when compared to tests of the same cells with mare plasma (chemotaxis, 11.6 +/- 2.91; phagocytosis, 3.94 +/- 0.269; P less than or equal to 0.005). PMNLs from neonatal foals responded with normal functions to plasma from normal adult horses. Results of both assays suggest that pre-colostral foal PMNLs are functionally mature but the expression of their chemotactic and phagocytic functions depends on the humoral source of chemotactic and opsonic factors.

Animals↗

Improved treatment of femoral shaft fractures in children. The "pontoon" 90-90 spica cast.

In the past 15 to 20 years, little improvement has been made in the standard treatment of femur fractures in children. Children younger than two years of age or weighing less than 30 pounds are normally treated with skin traction or immobilized in a plaster cast or both. Older or heavier children are often treated with skeletal traction, followed by early or late application of spica cast in the neutral position. A method of spica cast treatment that immobilizes the limb in the 90-90 position using a reinforced cast incorporating a distal femoral traction pin--the pontoon spica--allows for early cast application and discharge from the hospital and encourages early motion of the knee joint. A series of 23 femur fractures in 21 patients were treated with this method. This series is compared with a series of 38 fractures treated with conventional methods. The follow-up period ranged from three to 24 months. The pontoon method provided better results in control of alignment than the conventional method, with no greater discrepancy in leg lengths than generally observed after skin traction and hip spica casts. The average hospital cost reduction was 73%, or approximately $13,334. There were no major complications with the pontoon method, which is now a standard treatment for femoral fractures in children.

Casts, Surgical↗

Cavum vergae. Association with neurologic abnormality and diagnosis by magnetic resonance imaging.

Cavum vergae is a cavity posterior to the septum pellucidum whose clinical significance has previously been unclear. Ten children are described who presented with neurologic findings and were found to have a cavum vergae or cavum vergae and cavum septum pellucidum by brain computed tomographic (CT) scan. Of the ten patients, five had delayed development, four had macrocephaly, two had learning disabilities, two had abnormal electroencephalograms, and one had Apert's syndrome. No cases of cavum vergae were found in 50 children who had brain CT scans for head trauma. These observations suggest that cavum vergae is a nonspecific brain CT scan finding that can be associated with neurologic abnormality. The results of magnetic resonance imaging of one patient with cavum vergae are also described.

Brain↗

A quantitative method for the analysis of cell shape and locomotion.

A rapid, semiautomated system to quantitate and analyze leukocyte shape and locomotion was developed. Video images of moving leukocytes were obtained using a Vidicon camera mounted on a Nikon phase microscope. The video signal was either inputted directly, or indirectly via a video cassette recorder, to a Datacube video analog-digital, digital-analog converter. A Digital Equipment Corporation LSI 11/23 computer using the RT-11/TSX-Plus operating system and computer programs written in FORTRAN and MARCO assembly language permitted image segmentation, image display, and calculation of position, speed, direction of movement and orientation of each leukocyte at 10 s intervals. These data were stored on a winchester disk for subsequent evaluation of the leukocyte orientation, speed and direction of movement using statistical and graphical methods. The reproducibility of measurements made with the video system was tested by comparison with manual measurements; a correlation coefficient of 0.998 was obtained for the two methods. Rates of chemokinesis were then determined for unstimulated and chemokinetically stimulated polymorphonuclear leukocytes (PMNs) and found to average 12.8 micron/min and 18.1 micron/min, respectively. The high speed, ease of data analysis, and potential for multiparameter evaluation makes this system useful for directly evaluating leukocyte locomotion.

Cell Movement↗