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Biomedical subjects

A M Moore

Publications and source records attributed to A M Moore.

At least 19 recordsLinked to original sources
PubMed2006

Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial.

BACKGROUND: Gefitinib has demonstrated activity in patients with non-small cell lung cancer (NSCLC). Clinical trials have not demonstrated a relationship between response to gefitinib and over-expression of the epidermal growth factor receptor (EGFR). Although, EGFR is not over-expressed in small cell lung cancer (SCLC), we postulated that gefitinib might affect tumor growth through other mechanisms. Agents that are active in NSCLC usually are also effective in SCLC. METHODS: The primary objective was to assess the clinical control rate: complete response (CR) partial response (PR) and stable disease (SD > 90 days), of gefitinib in patients with chemo-resistant and chemo-sensitive small cell cancers. Eligibility criteria included pathologic proof of a neuroendocrine tumor, especially small cell cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, prior treatment with one or two prior chemotherapy regimens and adequate end-organ function. Patients received gefitinib, 250 mg p.o. daily until disease progression or intolerable side effects. RESULTS: From April 2003 to March 2004, 19 patients were enrolled. Small cell lung cancer accounted for 18 of the 19 patients and one patient had metastatic Merkel cell carcinoma. Twelve patients (63%) had chemo-sensitive disease, defined as progression greater than three months from completion of prior chemotherapy; 7 (37%) had chemo-refractory disease; 13 (68%) had one prior chemotherapy regimen. Other patient characteristics: mean age 64 years (range 52-79 years); ECOG PS 0/1/2 = 7/9/3, M:F = 9:10. Grade 3 toxicities included: fatigue in three patients (15.8%), pulmonary toxicities in three (15.8%) and one patient (5.3%) each with hyperglycemia or pain. Four patients had grade four toxicities: one patient (5.3%) with fatigue and three patients (15.8%) with dyspnea. There were no patients with grade 3 or 4 rash or diarrhea. Two patients had stable disease (<90 days) and 17 had progressive disease as their best response. This study was a two-stage design and because the continuing criterion for stage one was not met, stage 2 was not performed. Median time to progression (TTP) was 50 days (95% CI = 21-58 days). One year overall survival (OS) was 21% (95% CI = 6-45.6%). CONCLUSION: Although gefitinib has activity in select patients with NSCLC, this study failed to demonstrate benefit in patients with small cell lung cancer.

Aged↗
PubMed2005

Prenatal ultrasonography and neonatal imaging of complete cleft sternum: a case report.

The prenatal diagnosis of a complete cleft sternum was established in a fetus of a twin pregnancy at 22 weeks' gestation. We present the prenatal imaging and correlation with postnatal magnetic resonance imaging and high-resolution ultrasonography. Thinned and depressed midline anterior chest wall transmitting the cardiac pulsation was the clue to the diagnosis, and the defective sternum could be identified on close sonographic observation. Successful surgical correction was undertaken at 2 months of age. There were no major associated abnormalities such as ectopia cordis or midline abdominal wall defects.

Adult↗
PubMed2001

The effect of graded intake of glycyl-L-tyrosine on phenylalanine and tyrosine metabolism in parenterally fed neonates with an estimation of tyrosine requirement.

Although tyrosine is considered indispensable during the neonatal period, its poor solubility has limited its inclusion in parenteral amino acid solutions to less than 1% of total amino acids. Dipeptides of tyrosine are highly soluble, have been shown to be well used and safe in animal models and humans, and, therefore, may be used as an effective means of providing tyrosine in the parenterally fed neonate. The goal of the present study was to determine the tyrosine requirement of the parenterally fed neonate receiving graded intakes of glycyl-L-tyrosine as a source of tyrosine. Thirteen infants receiving adequate energy (340 +/- 38 kJ. kg(-1).d(-1)) and protein (2.4 +/- 0.4 g.kg(-1).d(-1)) were randomized to receive parenteral nutrition with one of five graded levels of glycyl-L-tyrosine. The mean requirement and safe level of intake were estimated using a 1-(13)C-phenylalanine tracer and linear regression cross-over analysis that identified a break point in the response of label appearance in breath CO(2) (F(13)CO(2)) and phenylalanine oxidation to graded tyrosine intake. Based on the mean estimates of whole-body phenylalanine oxidation, the tyrosine mean requirement and safe level of intake were found to be 74 mg.kg(-1). d(-1) and 94 mg.kg(-1).d(-1), respectively. This represents 3.1 and 3.9% of total amino acids, respectively, considerably higher than levels found in present commercially available pediatric amino acid solutions. These data raise concern regarding the adequacy of aromatic amino acid intake in the parenterally fed neonate.

Amino Acids↗
PubMed2001

Selective screening for neonatal galactosemia: an alternative approach.

UNLABELLED: No universal consensus exists for population-based neonatal screening for galactosemia. In our institution, selective screening for classical galactosemia is carried out on infants under 2 wk of age and those with symptoms suggestive of this disorder. Eighteen cases were diagnosed from 25,099 tests done; 17 were symptomatic at the time of diagnosis. CONCLUSION: We suggest that improved clinical vigilance and selective screening would identify most infants with severe galactosemia as early as a population-based program.

Biomarkers↗
PubMed2000

Deficiency of lamellar bodies in alveolar type II cells associated with fatal respiratory disease in a full-term infant.

We report a case of a full-term female infant who presented with severe respiratory distress shortly after birth and died at 23 d of age with unremitting respiratory failure. Infectious and other known causes of respiratory disease in this clinical setting were excluded. Examination of a lung biopsy showed abnormal lung parenchyma with features reminiscent of desquamative interstitial pneumonitis. Ultrastructural studies revealed that alveolar type II cells lacked cytoplasmic lamellar bodies, while other organelles appeared normal. Histochemical and immunohistochemical investigations indicated normal alveolar type II cell marker expression including surfactant proteins (SP-A, SP-B, pro-SP-B, and pro-SP-C). Mutations in the coding sequences of the SP-B gene were excluded as a cause of disease. This case appears to be a novel congenital defect affecting the pulmonary surfactant system. The cellular abnormality may involve the assembly of cytoplasmic lamellar bodies in alveolar type II cells-the principal storage site of pulmonary surfactant.

Biopsy↗
PubMed1999

Coupled ocean-atmosphere dynamics in the Indian Ocean during 1997-98.

Climate variability in the Indian Ocean region seems to be, in some aspects, independent of forcing by external phenomena such as the El Niño/Southern Oscillation. But the extent to which, and how, internal coupled ocean-atmosphere dynamics determine the state of the Indian Ocean system have not been resolved. Here we present a detailed analysis of the strong seasonal anomalies in sea surface temperatures, sea surface heights, precipitation and winds that occurred in the Indian Ocean region in 1997-98, and compare the results with the record of Indian Ocean climate variability over the past 40 years. We conclude that the 1997-98 anomalies--in spite of the coincidence with the strong El Niño/Southern Oscillation event--may primarily be an expression of internal dynamics, rather than a direct response to external influences. We propose a mechanism of ocean-atmosphere interaction governing the 1997-98 event that may represent a characteristic internal mode of the Indian Ocean climate system. In the Pacific Ocean, the identification of such a mode has led to successful predictions of El Niño; if the proposed Indian Ocean internal mode proves to be robust, there may be a similar potential for predictability of climate in the Indian Ocean region.

Journal Article↗
PubMed1999

Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes.

Dendritic cells (DCs) emigrate to regional lymph nodes (LNs) during immune responses via afferent lymphatic channels. Secondary lymphoid-tissue chemokine (SLC), a CC chemokine, is expressed in secondary lymphoid organs and mediates the chemotaxis of lymphocytes and DCs via its receptor, CC chemokine receptor 7 (CCR7). By dual-label fluorescence confocal microscopy, we showed MHC class II-positive cells within SLC-staining lymphatic channels in the mouse dermis. SLC was a potent in vitro chemoattractant for cultured, migratory skin DCs, and it enhanced the emigration of MHC class II-positive DCs from mouse skin explants by an average of 2.5-fold. Mature or cytokine-activated, but not resting, Langerhans cells expressed CCR7 mRNA by RT-PCR. Anti-SLC Abs, but not control or anti-eotaxin Abs, blocked the in vivo migration of 51Cr-labeled, skin-derived DCs from footpads to draining LNs by 50% (n = 9, p < 0. 005). Thus, we provide direct evidence that SLC and CCR7 participate in the emigration of DCs from peripheral tissue to LNs via lymphatics.

Animals↗
PubMed1999

Symptomatic hypoglycemia in otherwise healthy, breastfed term newborns.

Transient symptomatic neonatal hypoglycemia, a diagnosis that is made in the neonatal nursery, is not usually associated with apparently normal infants who have been discharged from hospital. We describe 3 such cases that presented at home on day 3 of life with seizures or life-threatening apneas. We postulate that early discharge of apparently normal infants with marginal nutritional or metabolic adaptation, may expose some infants to postdischarge (but still neonatal) hypoglycemia and its attendant risks.

Breast Feeding↗
PubMed1998

Phenylalanine and tyrosine metabolism in neonates receiving parenteral nutrition differing in pattern of amino acids.

Tyrosine is considered to be an indispensable dietary amino acid in the neonate, yet achieving adequate parenteral tyrosine intake is difficult due to its poor solubility. Increasing the supply of phenylalanine is the most common means of compensating for low tyrosine levels. Unfortunately, plasma phenylalanine concentrations are sometimes elevated in infants receiving high phenylalanine intake. This led us to study the phenylalanine and tyrosine metabolism in 16 neonates randomized to receive total parenteral nutrition with either a high or a moderate phenylalanine-containing amino acid solution. A primed, 24-h continuous stable isotope infusion of L-[1-13C]phenylalanine and L-[3,3-2H2]tyrosine was given to enable the measurement of phenylalanine and tyrosine kinetics. Results demonstrated that 1) phenylalanine hydroxylation was significantly greater in infants receiving high phenylalanine, 2) phenylalanine oxidation and percent dose oxidized was also significantly greater in infants receiving high phenylalanine, 3) apparent phenylalanine retention was greater in neonates receiving high phenylalanine, and 4) alternate catabolites of phenylalanine and tyrosine metabolism were significantly greater in infants receiving high phenylalanine compared with moderate phenylalanine. We conclude that neonates respond to increased parenteral phenylalanine intake by increasing their hydroxylation and oxidation rates. The greater oxidation of phenylalanine in infants receiving high phenylalanine in conjunction with the urinary excretion of alternate catabolites of phenylalanine and tyrosine suggests that the high phenylalanine intake may be in excess of needs. However, the lower apparent phenylalanine retention observed in infants receiving moderate phenylalanine suggests that the total aromatic amino acid level of moderate phenylalanine may be deficient for neonatal needs.

Amino Acids↗
PubMed1997

Changes in gastric emptying in early postnatal life.

OBJECTIVE: To study the pattern of gastric emptying in very premature infants and to determine whether there are changes with postnatal age and the ability to tolerate feedings. METHODS: Sequential ultrasound measurements of the gastric antral cross-sectional area were obtained in 32 infants (mean gestational age, 26 +/- 1 weeks) before and after feeding for 2 hours. Studies were carried out after initiation of feedings, when full feedings were received, and at 32 weeks. Infants classified as feeding intolerant (n = 9) were also studied when feedings were restarted. Gastric emptying was assessed by the time taken for antral cross-sectional area to reach maximal value and to decrease to half the maximal increment (half-antral clearance). RESULTS: Delayed antral distention was observed at the time of the initial study in both feeding-tolerant (8 of 23) and feeding-intolerant (8 of 9) infants; however, there were significant differences in times for maximal antral distention (p < 0.002) and half-antral clearance (p < 0.006) between the feeding-tolerant and feeding-intolerant infants. By the time of full feedings, the feeding-intolerant infants showed immediate gastric emptying but still had a longer half-antral clearance time (p < 0.01). By 32 weeks, all infants had immediate antral distention and a more mature curvilinear pattern of gastric emptying. CONCLUSIONS: Knowledge of these different patterns of gastric emptying in very premature infants may lead to the development of more rational feeding strategies.

Aorta, Abdominal↗
PubMed1997

Peripheral chemoreceptors in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) is a rare disorder of unknown etiology, characterized by failure of the autonomic control of respiration. The primary defect is believed to involve central respiratory control; however, no specific lesion has been identified. We report two cases of CCHS (one female, 3 mo of age and one male 2 yr of age) in which there was detailed examination of the neural, muscular, and chemoreceptor components of respiratory control. Although no specific abnormalities were identified in the central nervous system (CNS) or muscles of respiration, striking changes were observed in arterial chemoreceptors, carotid bodies (CB), and airway chemoreceptors, neuroepithelial bodies (NEB). In both cases, CB were small (< 50% of control), with a marked decrease in the number of glomus cells identified by immunostaining for tyrosine hydroxylase and serotonin. Ultrastructural analysis of glomus cells in Case 1 showed a marked decrease in the frequency of dense core vesicles (< 20% of control), the storage site of amine and peptide neurotransmitters. Immunostaining for S100 protein, a marker of sustentacular or Type II cells, was increased up to twofold compared with controls. In the lung, the frequency and size of NEB immunostained for bombesin was increased twofold in both cases, suggesting compensatory hyperplasia of airway chemoreceptors. Since intact peripheral chemoreceptors are essential for respiratory control, especially the response to hypoxia, abnormalities in CB and NEB may contribute to the pathophysiology of CCHS and related conditions such as sudden infant death syndrome (SIDS).

Bombesin↗
PubMed1995

Altered expression of type I collagen, TGF-beta 1, and related genes in rat lung exposed to 85% O2.

The gene expressions of type I collagen and transforming growth factor-beta 1 (TGF-beta 1) were studied in lung tissue of rats exposed to air or 85% O2 for 14 days. Peak expression of type I collagen mRNA was observed by 14 days of 85% O2 exposure, at the same time as maximal immunoreactive type I collagen, which was most marked surrounding the major airways and vessels. TGF-beta 1 mRNA also significantly increased after 14, but not 4 or 6 days of 85% O2 exposure. TGF-beta 1 immunoreactivity was only detected on day 14 of 85% O2 exposure and was localized primarily to the pulmonary epithelium. As an increase in immunoreactive type I collagen was evident by day 6 of O2 exposure, the gene expressions of interstitial collagenase (MMP-1), stromelysin, and the tissue inhibitor of the metalloproteinases (TIMP) were also examined. Increased mRNA expressions of interstitial collagenase and TIMP preceded those of type I collagen and TGF-beta 1, occurring at 4-6 days of exposure to 85% O2, while there was no significant change in stromelysin mRNA. These findings are compatible with the initial O2-mediated increase in type I collagen deposition being a result of an altered proteinase/antiproteinase balance in the lung, and the subsequent more marked deposition being a response to increased TGF-beta 1 synthesis.

Animals↗
PubMed1993

Cutis marmorata telangiectatica congenita.

Cutis marmorata telangiectatica congenita (CMTC) is an uncommon benign condition presenting at birth with levido reticularis, telangiectasia, phlebectasia, and possible ulceration of the involved skin. Diagnosis is made through the clinical picture and supported by characteristic histopathologic changes when present. This condition should not be confused with manifestations of serious system disease and aggressive treatment is not indicated. We describe in this report a case of CMTC.

Child, Preschool↗
PubMed1991

Anatomic, metabolic, neuropsychological, and molecular genetic studies of three pairs of identical twins discordant for dementia of the Alzheimer's type.

Three pairs of twins, each with proved monozygosity, were shown to be discordant for dementia of the Alzheimer's type and to have remained discordant for periods of 8 to 11 years. Dementia of the Alzheimer's type was demonstrated by history; serial clinical examinations; serial measurements of cerebral glucose utilization using positron emission tomography and of cerebral ventricular volumes and of rates of change of volumes using quantitative computed tomography; and by serial neuropsychological tests. The results of each of these measures showed no evidence of clinical abnormality in any unaffected twin. DNA markers from the proximal long arm of chromosome 21 did not distinguish between the affected and the unaffected member of any pair of identical twins. Family pedigrees were negative for Alzheimer's disease. The results suggest that environmental or other nongenetic factors contribute to Alzheimer's disease in discordant monozygotic twins, or that some cases arise by a postzygotic somatic mutation.

Aged↗
PubMed1991

Trot-gallop gait transitions in quadrupeds.

Although the kinematics, mechanics, energetics and mathematics of trot-gallop gait transitions have been discussed in previous papers, no one article has tried to assimilate all the information. This review paper does this and includes a summary of the relatively new engineering (mathematical) approach to analyzing these transitions developed by Schoner et al. (29). The paper also presents unpublished data on gait transitions in cats and monkeys, and attempts to develop some general principles pertaining to trot-gallop transitions. Finally, the paper highlights areas where additional information is needed.

Acceleration↗
PubMed1991

Transforming growth factor alpha: in vivo release by normal human skin following UV irradiation and abrasion.

Transforming growth factor alpha (TGF alpha) is a keratinocyte-growth-stimulating factor which may have a role in epidermal hyperproliferation, psoriasis, and wound healing. Since increased epidermal proliferation occurs in response to UV radiation, we have measured the amount of TGF alpha in exudates from normal and UVB-irradiated human skin. Cutaneous exudates were obtained using the skin chamber abrasion technique from one side of the back of volunteers (n = 10) with normal skin (collected following skin contact times of 2 and 30 min). Exudates were similarly obtained from the contralateral side of the back at sites irradiated 2 h previously with 3 x the minimum erythemal dose UVB. Levels of TGF alpha were measured by radioimmunoassay. Normal human skin released TGF alpha immediately after abrasion: unirradiated, 63 +/- 18 ng/ml; irradiated, 89 +/- 15 ng/ml. Levels of TGF alpha increased within 30 min to 110 +/- 14 ng/ml in unirradiated skin and to 190 +/- 17 ng/ml in irradiated skin. Irradiated sites at 30-min time points were significantly higher (p less than 0.05) than all other samples. The presence of releasable TGF alpha in normal skin suggests a role for TGF alpha in wound repair mechanisms.

Adolescent↗
PubMed1990

Reduced atrial contribution to left ventricular filling in patients with severe tricuspid regurgitation after tricuspid valvulectomy: a Doppler echocardiographic study.

Patients undergoing valvulectomy for isolated tricuspid valve endocarditis offer the unique opportunity to study the effects of acquired right ventricular volume overload on left ventricular filling in persons free of pulmonary hypertension and preexisting left heart disease. Eleven patients who had undergone total or partial removal of the tricuspid valve were compared with 11 age-matched control subjects; Doppler echocardiographic techniques were used to quantify changes in left ventricular filling and to relate them to changes in left ventricular and left atrial geometry caused by right ventricular and right atrial distension. The late diastolic fractional transmitral flow velocity integral, a measure of the left atrial contribution to left ventricular filling, was significantly decreased in patients undergoing tricuspid valvulectomy compared with control subjects (0.22 +/- 0.11 versus 0.32 +/- 0.09; p less than 0.04). Severe tricuspid regurgitation in these patients resulted in marked right atrial distension, reversal of the normal interatrial septal curvature and compression of the left atrium such that left atrial area was significantly smaller than in control subjects (5.9 +/- 2.2 versus 8.6 +/- 1.2 cm2/m2; p less than 0.005). Acting as a receiving chamber, the left ventricle was maximally compressed by the volume-overloaded right ventricle in late diastole, coincident with the timing of atrial systole, resulting in a significant increase in the left ventricular eccentricity index compared with that in control subjects (1.35 +/- 0.14 versus 1.03 +/- 0.1; p less than 0.001). Thus, right ventricular volume overload due to severe tricuspid regurgitation results in left heart geometric alterations that decrease left atrial preload, impair left ventricular receiving chamber characteristics and reduce the atrial contribution to total left ventricular filling.

Adult↗