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Biomedical subjects

P Maloney

Publications and source records attributed to P Maloney.

At least 19 recordsLinked to original sources
PubMed2005

Rare cancer cell analyzer for whole blood applications: automated nucleic acid purification in a microfluidic disposable card.

One current challenge facing point-of-care cancer detection is that existing methods make it difficult, time consuming and too costly to (1) collect relevant cell types directly from a patient sample, such as blood and (2) rapidly assay those cell types to determine the presence or absence of a particular type of cancer. We present a proof of principle method for an integrated, sample-to-result, point-of-care detection device that employs microfluidics technology, accepted assays, and a silica membrane for total RNA purification on a disposable, credit card sized laboratory-on-card ('lab card") device in which results are obtained in minutes. Both yield and quality of on-card purified total RNA, as determined by both LightCycler and standard reverse transcriptase amplification of G6PDH and BCR-ABL transcripts, were found to be better than or equal to accepted standard purification methods.

Fusion Proteins, bcr-abl↗
PubMed2005

Rare cancer cell analyzer for whole blood applications: microcytometer cell counting and sorting subcircuits.

We demonstrate sorting of rare cancer cells from blood using a thin ribbon monolayer of cells within a credit-card sized, microfluidic laboratory-on-a-card ("lab card") structure. This enables higher cell throughput per minute thereby speeding up cell interrogation. In this approach, multiple cells are viewed and sorted, not individually, but as a whole cell row or section of the ribbon at a time. Gated selection of only the cell rows containing a tagged rare cell provides enrichment of the rare cell relative to background blood cells. We also designed the cell injector for laminar flow antibody labeling within 20s. The approach combines rapid laminar flow cell labeling with monolayer cell sorting thereby enabling rare cell target detection at sensitivity levels 1000 to 10,000 times that of existing flow cytometers. Using this method, total cell labeling and data acquisition time on card may be reduced to a few minutes compared to 30-60 min for standard flow methods.

Antigens, CD34↗
PubMed2003

Allelic imbalance at the DNA mismatch repair loci, hMSH2, hMLH1, hPMS1, hPMS2 and hMSH3, in squamous cell carcinoma of the head and neck.

BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is one of the 10 most frequently occurring cancers in the world. Defective mismatch repair, as exhibited by the phenomenon of microsatellite instability, has been observed in SCCHN although no reports of mismatch repair gene mutations or altered protein expression have been published. In a variety of microsatellite instability (MSI) positive cancers where mutations in the mismatch repair (MMR) genes were not observed, allelic imbalance at the loci of the MMR genes was prevalent. OBJECTIVE: To investigate whether allelic imbalance at the MMR genetic loci contributes to the development of SCCHN. MATERIALS AND METHODS: 35 matched normal/tumour SCCHN pairs were studied using 29 microsatellite markers located within and adjacent to six known DNA mismatch repair genes. In addition, mutational analysis and protein expression of hMSH2 and hMLH1 were investigated. RESULTS AND CONCLUSIONS: We demonstrated that 36 and 17% of the analysed SCCHN specimens exhibited allele imbalance at the hMLH1 and hMSH3 genetic loci, respectively. Allelic instability at these two loci was found to be correlated with the MSI status of the SCCHN tumours. Allelic instability was found to be uncommon at the other MMR gene loci analysed. One mutation was found in hMSH2 and none in hMLH1 in this series of tumours. 23 of 24 (96%) of the examined SCCHN tumours showed reduced expression of either hMSH2 or hMCH1 genes. Allelic instability in the MMR genes, hMLH1 and hMSH3, is proposed to be involved in the aetiology of SCCHN tumours.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Cancer-specific genomic instability in bronchial lavage: a molecular tool for lung cancer detection.

We examined genomic instability in DNA from 80 bronchial lavage samples from patients with lung cancer and individuals with no malignant lung disease. We used a multiplex assay of eight fluorescent-tagged microsatellite markers that have a very high incidence of allelic imbalance in lung tumors. When genomic instability at individual loci was analyzed statistically against diagnosis, markers D3S1289 (P = 0.033), D3S1300 (P = 0.001), D13S171 (P = 0.009), and D17S2179E (P = 0.017) demonstrated significantly higher frequency of instability in bronchial lavage specimens from lung cancer cases than those with nonmalignant conditions. In contrast, markers D9S157, D9S161, D13S153, and D5S644 demonstrated lower specificity (P > 0.05) for lung tumors. These results suggest that genomic instability in some loci may be related to high proliferation rates but not necessarily to cell commitment to malignancy. When genomic instability was scored with only the four cancer-specific markers, the assay produced a sensitivity of 73.9% and a specificity of 76.5%. On combining the results from the cytological examination and the molecular assay, the sensitivity reached 82.6%. These results indicate that in our efforts to investigate genomic instability as a potential marker for the early detection of lung cancer, we need to identify cancer-specific genomic instability markers. This paper has shown that these first four markers may be considered to form an individual set of cancer-specific genomic instability markers.

Adult↗
PubMed2001

Chronic low back pain and depression in a sample of veterans.

The relationship between chronic low back pain and scores on depression was examined in a sample of 31 veterans who completed a depression inventory. Analysis indicated that those with chronic low back pain scored significantly higher on depression than those without.

Adult↗
PubMed2001

Loss of heterozygosity on chromosomes 3, 9, 13, and 17, including the retinoblastoma locus, in uveal melanoma.

PURPOSE: To identify tumor-suppressor loci that may contribute to the pathogenesis of uveal melanoma. METHODS: Multiplex fluorescence microsatellite assays were performed on 27 uveal melanomas using markers at 3p25-p26, 3p14.2, 9p21-p23, 13q14, 13q12.3-q13, and 17p13, close to or within the von Hippel Lindau (VHL), fragile histidine triad (FHIT), p16/cyclin-dependent kinase inhibitor 2 (CDKN2A), retinoblastoma (RB1), breast cancer 2 (BRCA2), and p53 tumor suppressor loci, respectively. Further markers on chromosomes 3 and 9 were analyzed individually. RESULTS: Loss of heterozygosity (LOH) was identified in 63% of tumors, most frequently on chromosome 3 (52%), in association with epithelioid cells (P = 0.0002) and microvascular loops (P = 0.0008). In the majority of cases, LOH on chromosome 3 was detected at all informative markers. The second most common alteration was LOH at an RB1 intragenic marker (21% tumors), with retention of a more centromeric 13q marker (near BRCA2). The pattern of LOH on chromosome 9p was consistent with the involvement of a region telomeric to CDKN2A. LOH at TP53 was infrequent. CONCLUSIONS: In the majority of cases, chromosome 3 LOH involves an entire chromosome homologue, which hampers identification of the relevant suppressor loci. This LOH correlates with the presence of microvascular loops and epithelioid cells, two of the recognized histologic indicators of poor prognosis. Data for chromosomes 13 and 9 support a role for RB1 in the pathogenesis of uveal melanoma but also raise the possibility of the involvement of additional loci close to RB1 and CDKN2A.

Acid Anhydride Hydrolases↗
PubMed2000

hMLH1 and hMSH2 expression correlates with allelic imbalance on chromosome 3p in non-small cell lung carcinomas.

DNA mismatch repair genes have been implicated in the pathogenesis and predisposition of certain malignancies through a mutator phenotype. In this study, we investigated, in 150 non-small cell lung carcinomas, the expression levels of hMLH1 and hMSH2 proteins in relation to loss of heterozygosity on chromosomes 3p and 2p, the mutational status of these genes' promoters and the hot spot exons. We have demonstrated that 88 of 150 (58.6%) tumor specimens had reduced expression levels of the hMLH1 protein, whereas 85 of 147 (57.8%) specimens had reduced expression levels of the hMSH2 protein. Reduced expression levels of both proteins were observed in 51 of 150 (34%) specimens. In adenocarcinomas, the reduction of hMSH2 expression was more frequently observed than that of hMLH1 (P<0.003), whereas in squamous cell carcinoma of the lung hMLH1 expression was more frequently reduced than hMSH2 (P<0.006). Reduced expression of hMLH1correlated with allelic imbalance on loci D3S1289 (P<0.0002) and D2S391 (P<0.05). It is of note that an inverse correlation was found between hMSH2 reduced expression and loss of heterozygosity at locus D3S1300 (P = 0.016). In addition, hMLH1 reduced expression was more frequently associated with heavy smokers, assessed by daily tobacco uptake (P = 0.018) and total smoking exposure (pack-years; P<0.05). In addition, a correlation between hMLH1 reduced expression and nodal metastasis in squamous cell carcinoma of the lung was observed (P = 0.015). No mutations were identified in the promoters or exons examined in these two genes. These findings indicate that hMLH1 and hMSH2 gene inactivation is a common event in the development of non-small cell lung carcinoma and allelic loss seems to be a major genetic event involved in hMLH1 silencing. In addition, we propose that a putative negative regulator of hMSH2 gene may be located at the locus 3p14.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Sensitivity and limitations of high throughput fluorescent microsatellite analysis for the detection of allelic imbalance: application in lung tumors.

We have used two hexaplex fluorescent microsatellite assays and analysis on an automatic sequencer to determine allelic imbalance in lung tumors. The markers used are located close to tumor-suppressor genes, DNA repair genes and regions frequently lost in lung cancer. We present a reference interval and quantify the reproducibility of the assays as assessed by multiple repeat reactions for normal DNAs. The cut-off value was calculated to 0.77 (23% reduction of one allele intensity) which, to the best of our knowledge, is currently the lowest reported cut-off. Using these parameters we analysed 85 lung carcinomas. Eighty-three samples (97.6%) showed allelic imbalance in at least one locus. It is of note that by using a selection of only 6 markers, imbalance was detected in 81 (95.2%) of the samples. Loci 9p21 and 9p23 exhibited the greatest imbalance (77% and 75% respectively). The fractional allele loss (FAL) for the 3p markers examined was greater in squamous cell carcinomas than adenocarcinomas (t-test, p=0.0001) while no such difference was observed for 9p. The degree of imbalance of different markers within the same sample was divergent, indicating heterogeneity of genomic status (losses, amplifications, aneuploidy) in these tumors. In conclusion, we have established a robust experimental platform with high throughput, sensitivity and specificity for the detection of allelic imbalance in lung tumors. Such assays may be useful for the detection of allelic imbalance in clinical samples to trace genetically abnormal cells and thus assist in the identification of individuals at a high risk for developing lung cancer.

Aged↗
PubMed1999

Is immobilization associated with an abnormal lipoprotein profile? Observations from a diverse cohort.

OBJECTIVE: The potential effects of ethnicity, gender, and adiposity on the serum lipid profile in persons with spinal cord injury (SCI) were determined. SUBJECTS: Subjects with SCI were recruited during their annual physical examination from Rancho Los Amigos Medical Center, Downey, California. Sedentary able-bodied controls were Bridge and Tunnel Officers of the Triboro Bridge and Tunnel Authority of the New York City metropolitan area. METHODS: Serum lipid profiles were investigated in 320 subjects with SCI and compared to those obtained from 303 relatively sedentary able-bodied controls. Serum lipid studies were obtained in the fasting state. Data were collected between 1993 and 1996. All lipid determinations were performed by the same commercial laboratory. MAIN OUTCOME MEASURES: The dependent variables were the values from the lipid profile analysis. The independent variables consisted of study group, gender, ethnic group, age, duration of injury, and anthropometric measurements. RESULTS: The serum high-density lipoprotein cholesterol (HDL-c) level was reduced in the SCI compared with the control group (mean+/-SEM) (42+/-0.79 vs 47+/-0.67 mg/dl, P<0.0005). The serum HDL-c level was significantly lower in males with SCI than males in the control group (39+/-0.83 vs 45+/-0.70 mg/dl, P<0.0001), but not for females (51+/-1.54 vs 54 1.52 mg/dl, n.s.). Within the subgroups for whites and Latinos, HDL-c values were also lower in subjects with SCI than in controls (whites: 41+/-1.02 vs 46+/-0.86 mg/dl, P<0.0001; Latinos: 37+/-1.53 vs 42+/-1.59 mg/dl, P<0.05), but not for African Americans (49+/-1.56 vs 51+/-1.27 mg/dl, n.s.). African Americans had higher HDL-c values than whites or Latinos (SCI: 49+/-1.56 vs 41+/-1.02 or 37+/-1.53 mg/dl, P< 0.0001; controls: 51+/-1.27 vs 46+/-0.86 mg/dl, P<0.01 or 42+/-1.59 mg/dl, P<0.0005). In persons with SCI, the serum HDL-c values were inversely related to body mass index and estimated per cent body fat (r=0.27, P<0.0001). CONCLUSION: In white and Latino males, but not in females or African Americans, immobilization from SCI appears to be associated with lower HDL-c values than in controls.

Adult↗
PubMed1998

Ethnicity effect on the serum lipid profile in persons with spinal cord injury.

OBJECTIVE: The potential effect of ethnicity on the serum lipid profile and lipoprotein(a) [Lp(a)] was studied in a population with chronic spinal cord injury (SCI). STUDY DESIGN: The distribution and correlates of high density lipoprotein (HDL) cholesterol and Lp(a) were studied in a population of 600 subjects with chronic SCI. RESULTS: Mean +/- SEM serum HDL cholesterol was significantly higher in the African American group than in the white and Latino groups (47 +/- 1 vs 40 +/- 1 and 38 +/- 1 mg/dL, p < .0001, respectively). The African American group had a lower serum total to HDL cholesterol ratio than white and Latino groups (4.46 +/- .153 vs 5.18 +/- .168 and 5.40 +/- .140 mg/dL, p < .01, respectively). Mean serum Lp(a) levels were significantly higher in the African American group than in Latino or white groups (29 +/- 2 vs 18 +/- 1 and 15 +/- 1 mg/dL, p < .0001, respectively). Age, duration of SCI, and level and completeness of lesion had no significant effect on serum Lp(a) level. CONCLUSIONS: In a population with chronic SCI, those in the African American group had the highest serum HDL cholesterol concentrations, the lowest serum total to HDL cholesterol ratios, and elevated levels of serum Lp(a) compared with the Latino and white groups. In a population of individuals with chronic SCI, ethnicity was shown to have a major effect on serum lipids and may be used to assist in the determination of cardiovascular risk.

Adult↗
PubMed1998

Lidocaine toxicity.

Local anesthetics are the most commonly used drugs in dentistry. The number of adverse reactions reported, particularly toxic reactions, are extraordinarily negligible. This article reports a case of lidocaine toxicity with its typical manifestation in a 37-yr-old healthy male. The toxic reaction followed transoral/transpharyngeal topical spraying of lidocaine preoperatively during preparation for general anesthesia. A review of dosages of the most commonly used local anesthetic drugs in dentistry and the management of a toxic reaction is presented. Clinicians need to be in a position to recognize and successfully manage this potential adverse reaction.

Administration, Topical↗
PubMed1995

Comparison of 10% povidone-iodine and 0.5% chlorhexidine gluconate for the prevention of peripheral intravenous catheter colonization in neonates: a prospective trial.

The purpose of the study was to compare the efficacy of 10% povidone-iodine with that of 0.5% chlorhexidine gluconate in 70% isopropyl alcohol for the prevention of peripheral intravenous catheter colonization in neonates. This was a multicenter, nonrandomized prospective study in a tertiary neonatal intensive care setting in which povidone-iodine and chlorhexidine gluconate were each used as antiseptic skin preparations over sequential 6-month periods. During the first 6 months of the study when povidone-iodine was in use 9.3% (38 of 408) of catheters were colonized. During the second 6 months of the study when chlorhexidine gluconate was in use, catheter colonization occurred in 4.7% (20 of 418, P = 0.01). Catheter-related bacteremia occurred during only 0.2% (2 of 826) of all catheterizations. Heavy skin colonization before catheter insertion (relative risk, 3.6; 95% confidence interval, 1.9, 7.0), catheterization > or = 72 hours (relative risk. 2.0; 95% confidence interval, 1.01, 3.8) and gestational age < or = 32 weeks (relative risk, 1.8; 95% confidence interval, 1.02, 3.3) increased colonization risk. Ampicillin infusion (relative risk, 0.4; 95% confidence interval, 0.2, 0.7) and 0.5% chlorhexidine gluconate cutaneous antisepsis (relative risk, 0.4; 95% confidence interval, 0.2, 0.8) were factors associated with decreased colonization risk. We conclude that 0.5% chlorhexidine gluconate in 70% isopropyl alcohol appears to be more efficacious than 10% povidone-iodine for the prevention of peripheral intravenous catheter colonization in neonates.

Analysis of Variance↗
PubMed1990

Predicting normal age-related changes with intelligence, projective, and perceptual-motor test variables.

From four tests, the WAIS, Rorschach, Hand Test, and Bender-Gestalt, 67 variables were derived and used to predict age for 240 individuals. Ages ranged from 15 to 65 yr., divided into five age intervals, with 48 subjects per group. 36 variables correlating with age were further reduced to 12 by means of a stepwise multiple R. A final R of .73 was obtained, accounting for 53% of the variance. While variables from all four of these tests correlated with the criterion, most of the significant variance could be attributed to intellectual factors.

Adolescent↗
PubMed1990

Chiropractic adjustive manipulation on subjects with acute low back pain: visual analog pain scores and plasma beta-endorphin levels.

The purpose of this study was to evaluate pain scores and plasma beta-endorphin levels following a single spinal adjustive manipulation in subjects with acute low back pain. Eighteen subjects were randomly assigned to either a control group, which received no treatment; a sham group, which received only light physical contact (touch); or an experimental group, which received an adjustive manipulation at a specific lumbar segment. Following a standard protocol, all subjects were administered visual analog pain scales and venous blood was drawn 5 min prior to, 5 min after, and 30 min after intervention. Analysis of the pain scores indicated that there was a slight, but significant, reduction of pain in the experimental group, but no similar reduction in the control or sham groups. Furthermore, this reduction of pain in the experimental group was not accompanied any significant change in the plasma beta-endorphin concentration.

Adult↗
PubMed1988

Post-ictal blood pressure in aneurysmal subarachnoid haemorrhage.

A prospective study in which the effect of the post-ictal systemic blood pressure levels on the outcome following surgically treated aneurysmal subarachnoid haemorrhage (SAH) in 325 patients is reported. No differentiation was made between pre-existing essential and prolonged reactive hypertension. A significant association was found between the trend for rising diastolic blood pressure levels and the tendency towards a poor outcome. There was a similar trend for rising systolic blood pressure levels which did not reach statistical significance. Patients with definite hypertension (blood pressure of 160/95 mmHg or greater) were 1.6 times as likely to have a poor outcome than were those with lower blood pressures.

Adult↗
PubMed1988

Recurrent aneurysmal subarachnoid haemorrhage: incidence, timing and effects. A re-appraisal in a surgical series.

A series of 510 patients with proven aneurysmal subarachnoid haemorrhage (SAH) is reported. The incidence of recurrent haemorrhage during the period awaiting surgery was 13.7%. There was no significant difference in incidence between good and poor grade patients. Following rebleeding there was an immediate mortality of 34% in good grade patients and 52% in poor grade patients. In the long term only 44.4% of good grade and 8% of poor grade patients made a good recovery following a second bleed as compared to 70.6% and 52.8% respectively for those who did not rehaemorrhage.

Humans↗