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Biomedical subjects

J Reilly

Publications and source records attributed to J Reilly.

At least 55 records · Page 3Linked to original sources

Myelofibrosis with myeloid metaplasia in young individuals: disease characteristics, prognostic factors and identification of risk groups.

Myelofibrosis with myeloid metaplasia (MMM) is an uncommon disorder in young individuals, for whom haemopoietic stem cell transplantation offers the only possibility of cure. However, although the latter procedure is associated with significant morbidity and mortality, the clinical course of MMM is variable, with some patients surviving for less than a year and others showing an indolent course. Selection of young MMM patients for transplantation or other newer therapies is currently difficult since no prognostic data exists for this subgroup. In the present collaborative study a number of initial clinical and laboratory parameters have been evaluated for prognosis in 121 MMM patients aged 55 years or less. Median survival of the series was 128 months (95% CI 90-172). In the Cox proportional hazard regression model three initial variables were independently associated with shorter survival: Hb <10 g/dl (P <0.0001), the presence of constitutional symptoms (fever, sweats, weight loss) (P=0.001), and circulating blasts >/=1% (P=0.003). Based on the above three criteria, of the 116 patients with complete data, two groups were identified: a 'low-risk' group, characterized by 88 patients with up to one adverse prognostic factor, in whom MMM had an indolent course (median survival 176 months, 95% CI 130-188), and a 'high-risk' group, including 28 patients with two or three factors, who had a more aggressive disease (median survival 33 months, 95% CI 20-42). The above prognostic scoring system showed a high positive predictive value, sensitivity and specificity to predict survival in the series, and could be of help in making treatment decisions in young patients with MMM.

Cause of Death↗

Preoperative screening for lung volume reduction surgery: usefulness of combining thin-section CT with physiologic assessment.

OBJECTIVE: This study was performed to assess the usefulness of preoperative thin-section CT alone and in combination with physiologic measurements in emphysema patients being evaluated for lung volume reduction surgery. SUBJECTS AND METHODS: Six 1-mm collimation sections through the chest were obtained in 20 patients being evaluated for lung volume reduction surgery. Extent and severity of emphysema were assessed by visually scoring the images. CT scores ranged from 0 to 144. Inspiratory resistance was measured in 12 of 20 patients and was also used to discriminate between responders (change in forced expiratory volume in 1 sec, > or = 150 ml after surgery) and nonresponders (change in forced expiratory volume in 1 sec, < 150 ml after surgery). RESULTS: Four of 20 patients with mild emphysema as revealed by thin-section CT (scores of < 50) did not improve lung function after lung volume reduction surgery. Eight of the remaining 16 patients with moderate to severe emphysema as revealed by thin-section CT (scores of > 50) underwent inspiratory resistance measurement. Those seven patients whose inspiratory resistance measurement exceeded 8.5 cm H2O/l per second did not respond favorably to lung volume reduction surgery (change in forced expiratory volume in 1 sec, < 150 ml). The remaining five patients whose inspiratory resistance measurement was less than 8.5 cm H2O/l per second responded favorably to lung volume reduction surgery. Thus, only five of the 20 patients showed improvement in forced expiratory volume in 1 sec after surgery. CONCLUSION: Our data suggest that among patients with moderate to severe emphysema who are being examined for lung volume reduction surgery, the combination of radiologic and physiologic assessment is more accurate for predicting a favorable response to lung volume reduction surgery than radiologic assessment alone. However, in patients with chronic obstructive pulmonary disease by the American Thoracic Society criteria, mild emphysema as revealed on thin-section CT virtually precludes further workup because these patients are unlikely to respond favorably to lung volume reduction surgery.

Adult↗

Repetitive bone marrow transplantation in nonmyeloablated recipients.

Transplantation of 200 million male BALB/c marrow cells into normal nonmyeloablated female BALB/c hosts results in relatively high levels of engraftment, whether the cells are infused repetitively over time or in a single infusion. These high engraftment rates suggested that repetitive injections of high levels of male BALB/c cells might be able to totally replace host marrow. Accordingly, we transplanted 40x10(6) male BALB/c bone marrow cells into female BALB/c recipients over a 7-week period for a total of 20 injections (800x10[6] marrow cells). Engraftment in this experimental group was compared to that seen when female recipients received 2x10(6) male marrow cells or phosphate-buffered saline (PBS) over the same injection schedule. Engraftment was quantitated at 5 and 7 weeks after the final infusion by detection of male-specific sequences in female host marrow, spleen, and thymus by Southern blot analysis using a Y-specific cDNA probe. Male DNA levels were quantitated with a Molecular Dynamics phosphorimager. Engraftment of male cells into female marrow at 5 and 7 weeks posttransplantation ranged from 19 to 88%, whereas that in spleen and thymus ranged between 30 and 100% and 28 and 50%, respectively. The mean percent engraftments for marrow, spleen, and thymus were 41, 69, and 39%, respectively. Mean percent engraftments for 2x10(6) cell infusions at 5 and 7 weeks for marrow, spleen, and thymus were 4, 6, and 4%, respectively. Marrow and spleen cellularity and total high proliferative potential colony-forming cell numbers were determined in PBS- and cell-injected mice. No significant differences between these groups were observed. For marrow engraftment, 20 injections of 40x10(6) cells was not more effective than five, but donor DNA in thymus and spleen was increased with 20 injections. Primitive progenitor cell levels and marrow cellularity do not increase in mice injected with large numbers of marrow cells, suggesting that host marrow cells are replaced rather than augmented by infused donor cells.

Animals↗

Chiaroscuro hematopoietic stem cell.

These observations suggest several immediate clinical strategies. In gene therapy, approaches could be targeted to obtain cycling of hematopoietic stem cells and gene-carrying retrovirus vector integration followed by engraftment at an appropriate time interval which favors engraftment. The same type of approach can be utilized for stem cell expansion approaches. Alternatively marrow or peripheral stem cell engraftment can be obtained with minimal to no toxicity in allochimeric strategies in such diseases as sickle cell anemia or thalassemia. A similar approach could be useful in obtaining cell engraftment with minimal toxicity in therapies employing cellular immune (T-cell and NK-cell) attack against cancer. These areas of clinical application are outline in Table 3.

Animals↗

The effect of African-American acculturation on neuropsychological test performance in normal and HIV-positive individuals. The HIV Neurobehavioral Research Center (HNRC) Group.

Two studies were conducted to examine the relationship of acculturation to neuropsychological test performance among (1) medically healthy, neurologically normal African Americans (N = 170); and (2) HIV positive (HIV+) subgroups of African Americans and Whites (Ns = 20) matched on age, education, sex, and HIV disease stage. Acculturation was measured through self report for all participants, and linguistic behavior (Black English use) was assessed in a subset of medically healthy individuals (N = 25). After controlling for the effects of age, education, and sex, medically healthy African Americans who reported less acculturation obtained lower scores on the WAIS-R Information subtest and the Boston Naming Test than did more acculturated individuals. Black English use was associated with poor performance on Trails B and the WAIS-R Information subtest. HIV+ African Americans scored significantly lower than their HIV+ White counterparts on the Category Test, Trails B, WAIS-R Block Design and Vocabulary subtests, and the learning components of the Story and Figure Memory Tests. However, after accounting for acculturation, ethnic group differences on all measures but Story Learning became nonsignificant. These results suggest that there are cultural differences within ethnic groups that relate to neuropsychological test performance, and that accounting for acculturation may improve the diagnostic accuracy of certain neuropsychological tests.

Acculturation↗

Engraftment of hematopoietic stem cells in nonmyeloablated and myeloablated hosts.

Hematopoietic stem cell engraftment has traditionally been assessed in irradiated murine hosts. More recently, we and others have shown that engraftment is virtually quantitative in host animals who have received no preconditioning myeloablation. It appears that at the stem cell level, engraftment may even be favored in the normal host. The final phenotypic readout in the engrafted animal is then determined by competition between the engrafted stem cells and the number of residual host stem cells. Further studies have indicated that with cytokine exposure in vitro, in vivo or 5-fluorouracil exposure and consequent stimulation of primitive hematopoietic stem cells to enter cell cycle, an engraftment defect relating to long-term engraftment occurs. This occurs in the face of an expansion of cycling surrogate stem cells as mirrored by the high proliferative potential colony-forming cell. These data indicate that the phenotype of the hematopoietic stem cell, as assessed in vitro, may not give insight into the phenotype of these cells in vivo.

Animals↗

Sex differences in visual recognition memory: support for a sex-related difference in attention in adults and children.

The selectivity hypothesis of Meyers-Levy (1989) proposes that cognitive sex differences reflect underlying differences in information processing between males and females. Males are considered to be more likely to organize information in a self-related manner, whereas females are more likely to adopt a comprehensive approach to information processing. We tested this hypothesis in children (10-15 years) and adults using recognition memory tasks. Tests were devised which employed male-oriented objects, female oriented objects, or random objects. In both the child and adult samples, females performed significantly better than males on tests using random and female-oriented objects. Males performed at the level of females only when tested for recognition of male-oriented objects. These results demonstrate that this sex difference is present prior to puberty and support the concept of sex differences in information processing.

Adolescent↗

In vitro cell density-dependent clonal growth of EGF-responsive murine neural progenitor cells under serum-free conditions.

Neural progenitor cell populations responsive to epidermal growth factor (EGF) have been shown to have proliferative potential and give rise to neurons, astrocytes, and oligodendrocytes. We have characterized EGF-responsive neural progenitor cells that give rise to bilineage neuronal/glial colonies (colony-forming unit neuron-glia; CFU-NeGl) and unilineage neuronal colonies (CFU-Ne). Clonality was confirmed utilizing mixtures of brain cells from Balb/c and ROSA26 (transgenic for beta-galactosidase) mice. With a few exceptions, colonies showed either all blue cells or all clear cells after staining with X-Gal. Clonal growth was analyzed after 10-11 days in relation to cell density by determining colony size and plating efficiency. Growth was density dependent (no growth below 10,000 cell/ml) and thus single cell cloning was not accomplished. An average plating efficiency of 4% was found for EGF-responsive neural cells derived from day 15-18 murine embryos when cultured at 12,500 to 200,000 cells/ml. Similar results were obtained with 1-day-old postnatal neural cells. When colonies were categorized by size, the relative number of colonies over 50 cells appeared to be maximum at 50,000 plated cells/ml. After 11 days in culture, 94, 96, and 78% of the colonies contained cells that expressed nestin, neurofilament, and GFAP, respectively. Double-label experiments revealed that > 62% of the colonies contained both GFAP and neurofilament expressing cells. These studies establish the existence of at least two populations of clonal neural progenitors: CFU-Ne and CFU-NeGl in fetal and postnatal murine brain.

Agar↗

Pediatric aerodigestive foreign body injuries are complications related to timeliness of diagnosis.

Foreign body (FB) injury from aspiration or ingestion is a common pediatric health problem. Diagnosis relies on clinical judgment plus medical history, physical examination, and radiographic evaluation. A multi-institutional review of 1269 FB events revealed that 85% were correctly diagnosed following a single physician encounter. However, 15% of the children had an elusive diagnosis (>1 week), despite previous evaluation. Delays in diagnosis were seven times more likely to occur in aspirations than in ingestions. Secondary injuries (e.g., pneumonia and atelectasis) occurred in 13% of airway FBs but in only 1.7% of esophageal FBs. Plain radiographs were used in 82% of children, and special studies (e.g., fluoroscopy) in only 7%. We conclude that diagnosis of FB injury in children is frequently achieved at the initial evaluation but that continued surveillance by follow-up visits to health care facilities from parents and other caretakers is important, to reduce pulmonary injuries.

Adolescent↗

Tobacco use assessment is a new, vital sign in dentistry.

The oral health effects of tobacco use are well documented. It is important that the oral health team become involved in decreasing tobacco use and preventing future use among their patients. By following a simple model for tobacco control education, such as the National Cancer Institute model, the oral health team can make a significant contribution toward improving the health of their patient.

Adolescent↗

Improved engraftment of human cord blood stem cells in NOD/LtSz-scid/scid mice after irradiation or multiple-day injections into unirradiated recipients.

Human lymphoematopoietic stem cells engraft in irradiated immunodeficient mice that are homozygous for the severe combined immunodeficiency (scid) mutation. Engraftment levels in C.B-17-scid/scid mice, however, have been low and transient, decreasing the utility of this model for investigation of the development potential and function of human stem cells. In the present study, we have used NOD/LtSz-scid/scid mice as recipients and human cord blood as a source of donor stem cells. Our results demonstrate that NOD/LtSz-scid/scid mice support approximately fivefold higher levels of human stem cell marrow engraftment than do C.B-17-scid/scid mice. Human CD34+ cells are present in the marrow of recipient mice, and the engrafted cells readily peripheralize to the circulation of the host. Terminal differentiation of the stem and progenitor cells into mature progeny is limited. Using a multiple-day injection protocol developed in mice, which allows engraftment of stem cells between congenic mice in the absence of irradiation preconditioning, we observed high levels of human cell engraftment in unirradiated NOD/LtSz-scid/scid recipients after three or five consecutive-day injections. These results demonstrate that NOD/LtSz-scid/scid mice support high levels of human stem cell engraftment and that xenogeneic lymphohematopoietic stem cells can engraft in unirradiated hosts without the need for ablative reconditioning. This model will be useful for the in vivo investigation of human stem cells and for the preclinical analysis of human stem cells for transplantation.

Animals↗

Developmental and stylistic variation in the composition of early vocabulary.

Results are reported for stylistic and developmental aspects of vocabulary composition for 1,803 children and families who participated in the tri-city norming of a new parental report instrument, the MacArthur Communicative Development Inventories. We replicate previous studies with small samples showing extensive variation in use of common nouns between age 0; 8 and 1;4 (i.e. 'referential style'), and in the proportion of vocabulary made up of closed-class words between 1;4 and 2;6 (i.e. 'analytic' vs. 'holistic' style). However, both style dimensions are confounded with developmental changes in the composition of the lexicon, including three 'waves' of reorganization: (I) an initial increase in percentage of common nouns from 0 to 100 words, followed by a proportional decrease; (2) a slow linear increase in verbs and other predicates, with the greatest gains taking place between 100 and 400 words; (3) no proportional development at all in the use of closed-class vocabulary between 0 and 400 words, followed by a sharp increase from 400 to 680 words. When developmental changes in noun use are controlled, referential-style measures do not show the association with developmental precocity reported in previous studies, although these scores are related to maternal education. By contrast, when developmental changes in grammatical function word use are controlled, high closed-class scores are associated with a slower rate of development. We suggest that younger children may have less perceptual acuity and/or shorter memory spans than older children with the same vocabulary size. As a result, the younger children may ignore unstressed function words until a later point in development while the older children tend to reproduce perceptual details that they do not yet understand. Longitudinal data show that early use of function words (under 400 words) is not related to grammatical levels after the 400-word point, confirming our 'stylistic' interpretation of early closed-class usage. We close with recommendations for the unconfounding of stylistic and developmental variance in research on individual differences in language development, and provide look-up tables that will permit other investigators to pull these aspects apart.

Child Language↗

Penetration of cefprozil into middle ear fluid of patients with otitis media.

Penetration of cefprozil into the middle ear fluid was investigated in patients with chronic otitis media. A total of 89 patients ranging from 7 months to 11 years old participated in the study. The middle ear fluid was removed by ventilation tubes inserted through the tympanic membrane at times ranging from 0.38 to 5.97 h after oral administration of a single dose of 15 or 20 mg/kg of body weight. A blood sample was also collected as soon as the middle ear fluid was removed. Plasma samples were analyzed for the concentration of cefprozil by a high-performance liquid chromatographic assay. Middle ear fluid samples were analyzed for the concentration of cefprozil by a microbiological assay. The concentrations of cefprozil in plasma ranged from 0.38 to 15.97 micrograms/ml at the 15-mg/kg dose level and from 1.28 to 21.47 micrograms/ml at the 20-mg/kg dose level. The corresponding middle ear fluid concentrations of cefprozil ranged from 0.06 to 4.44 micrograms/ml and from 0.17 to 8.67 micrograms/ml, respectively. Cefprozil penetrates well into middle ear fluid in patients with chronic otitis media.

Cephalosporins↗

Engraftment of normal murine marrow into nonmyeloablated host mice.

When 200 x 10(6) male BALB/c cells are given by tail vein injection to female nonmyeloablated hosts in one injection, a relatively low engraftment percentage is seen, but when the same total number of cells is given over five injections (separated by 24 hours), the observed engraftment is much higher. A further increase in engraftment appears to occur when the same number of cells is given in 10 injections separated by at least 24 hours. These data suggest that somewhere between 5 and 10% of marrow niches are available at intervals of 24 or more hours and that the keys to high levels of engraftment are the cell cycle status of the engrafting stem cell and the schedule of engraftment.

Animals↗

Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways.

Recent discoveries suggesting essential bioactivities of nitric oxide (NO.) in the lung are difficult to reconcile with the established pulmonary cytotoxicity of this common air pollutant. These conflicting observations suggest that metabolic intermediaries may exist in the lung to modulate the bioactivity and toxicity of NO.. We report that S-nitrosothiols (RS-NO), predominantly the adduct with glutathione, are present at nano- to micromolar concentrations in the airways of normal subjects and that their levels vary in different human pathophysiologic states. These endogenous RS-NO are long-lived, potent relaxants of human airways under physiological O2 concentrations. Moreover, RS-NO form in high concentrations upon administration of NO. gas. Nitrite (10-20 microM) is found in airway lining fluid in concentrations linearly proportional to leukocyte counts, suggestive of local NO. metabolism. NO. itself was not detected either free in solution or in complexes with transition metals. These observations may provide insight into the means by which NO. is packaged in biological systems to preserve its bioactivity and limit its potential O2-dependent toxicity and suggest an important role for NO. in regulation of airway luminal homeostasis.

Adolescent↗

Penetration of cefprozil into tonsillar and adenoidal tissues.

Penetration of cefprozil into tonsillar and/or adenoidal tissues was investigated for patients undergoing tonsillectomy and/or adenoidectomy. A total of 29 patients ranging in age from 2 to 14 years participated in the study. The tonsils and/or the adenoids were removed at times ranging from 0.33 to 3.17 h after oral administration of a dose of either 7.5 or 20 mg/kg of body weight. A blood sample was also collected as soon as the tissue sample was removed. Plasma, tonsil, and adenoid samples were analyzed for cis and trans isomers of cefprozil by high-performance liquid chromatographic assays. The concentrations of the cis isomer of cefprozil in plasma ranged from 0.60 to 9.87 micrograms/ml at the 7.5-mg/kg dose level and from 1.04 to 20.40 micrograms/ml at the 20-mg/kg dose level. The corresponding concentrations of the cis isomer in tonsil tissue ranged from 0.48 to 2.42 micrograms/g and from 1.00 to 4.29 micrograms/g, respectively. The corresponding concentrations of the cis isomer in adenoid tissue ranged from 0.40 to 4.20 micrograms/g and from 1.74 to 4.94 micrograms/g, respectively. The concentrations of the trans isomer were about 1/10 of those observed for the cis isomer. The median ratios of the cefprozil concentration in tonsillar tissue to that in plasma were 0.37 and 0.47 for patients receiving a 7.5- or a 20-mg/kg oral dose of cefprozil, respectively. The corresponding median ratios for the adenoidal tissue were 0.46 and 0.82, respectively. The cefprozil concentrations in either the tonsillar or the adenoidal tissue at both dose levels over 3.17 h after dosing are much higher than the MICs for common pathogens which cause pharyngitis or tonsillitis.

Adenoidectomy↗

Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance.

BACKGROUND: Insulin resistance and impaired insulin secretion both occur in non-insulin-dependent diabetes (NIDDM), but their relative importance is unclear. Hyperglycemia itself has adverse effects on tissue insulin sensitivity and insulin secretion that make it difficult to distinguish between primary and secondary abnormalities. To avoid this problem we studied subjects with postprandial glucose intolerance but not sustained hyperglycemia. METHODS: We compared the rate of systemic appearance and disappearance of glucose, the output of endogenous hepatic glucose, splanchnic and muscle uptake of glucose, and plasma insulin and glucagon responses after the ingestion of 1 g of glucose per kilogram of body weight in 15 subjects with impaired glucose tolerance (8 of them nonobese and 7 obese) and in 16 normal subjects (9 nonobese and 7 obese) who were matched for age and weight. RESULTS: After glucose ingestion the mean (+/- SE) rate of total systemic appearance of glucose was significantly higher in both the nonobese subjects (455 +/- 12 mmol per five hours) and the obese subjects (486 +/- 17 mmol per five hours) with impaired glucose tolerance than in the respective normal subjects (411 +/- 11 and 436 +/- 7 mmol per five hours). This difference was fully accounted for by the reduced suppression of endogenous hepatic glucose in the subjects with impaired glucose tolerance (a reduction of about 28 percent, vs. 48 percent in the normal subjects; P less than 0.01). Despite late hyperinsulinemia, at 30 minutes the subjects with impaired glucose tolerance had smaller increases in plasma insulin and smaller reductions in plasma glucagon (both P less than 0.01). Molar ratios of plasma insulin to plasma glucagon levels correlated inversely (r = -0.62, P less than 0.001) with the rates of systemic glucose appearance; the latter correlated positively (r = 0.72, P less than 0.0001) with peak plasma glucose concentrations. CONCLUSIONS: Impaired glucose tolerance, the precursor of NIDDM, results primarily from reduced suppression of hepatic glucose output due to abnormal pancreatic islet-cell function. The late hyperinsulinemia may be the consequence of an inadequate early beta-cell response rather than of insulin resistance.

Blood Glucose↗