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Biomedical subjects

M Cullen

Publications and source records attributed to M Cullen.

At least 19 recordsLinked to original sources
PubMed2005

Intravenous immunoglobulin for resistant Clostridium difficile infection.

Clostridium difficile (CD)-associated diarrhoea and colitis may relapse in up to 20% of treated patients. We present a patient who failed to respond over a 6-month period to treatment either singly or in combination with metronidazole, vancomycin, rifampicin, cholestyramine and probiotics. Her diarrhoea rapidly resolved after a 3-day course of intravenous immunoglobulin. This treatment may compensate for a failed immune response to CD toxin and should be considered for relapsing CD-associated diarrhoea where there is no response to conventional treatment strategies.

Clostridioides difficile↗
PubMed2005

The development of gemcitabine and carboplatin in the treatment of non-small-cell lung cancer.

Gemcitabine plus carboplatin is a widely used regimen for the treatment of advanced non-small-cell lung cancer (NSCLC). This two drug combination is effective, with a favorable safety profile, and is well tolerated in the outpatient setting. Gemcitabine/carboplatin prolongs survival compared with gemcitabine alone, but with greater hematological toxicity. The combination regimen appears to be superior to or equally effective as other regimens including mitomycin, ifosfamide and cisplatin (MIC), cisplatin/vinblastine, gemcitabine/paclitaxel, paclitaxel/carboplatin and gemcitabine/cisplatin. Gemcitabine combined with carboplatin is associated with more hematological toxicity, but the incidence of non-hematological toxicity is often significantly lower. Gemcitabine/carboplatin also improves patient quality of life, supporting its use in treating patients with advanced NSCLC in the outpatient setting.

Aged↗
PubMed2004

Determinants of isocyanate exposures in auto body repair and refinishing shops.

As part of the Survey of Painters and Repairers of Auto bodies by Yale (SPRAY), the determinants of isocyanate exposure in auto body repair shops were evaluated. Measurements (n = 380) of hexamethylene diisocyanate-based monomer and polyisocyanate and isophorone diisocyanate-based polyisocyanate were collected from 33 auto body shops. The median total reactive isocyanate concentrations expressed as mass concentration of the NCO functional group were: 206 microg NCO/m3 for spray operations; 0.93 microg NCO/m3 for samples collected in the vicinity of spray operations done on the shop floor (near spray); 0.05 microg NCO/m3 for office or other shop areas adjacent to spray areas (workplace background); 0.17 microg NCO/m3 for paint mixing and gun cleaning operations (mixing); 0.27 microg NCO/m3 for sanding operations. Exposure determinants for the sample NCO mass load were identified using linear regression, tobit regression and logistic regression models. For spray samples in a spray booth the significant determinants were the number of milliliters of NCO applied, the gallons of clear coat used by the shop each month and the type of spray booth used (custom built crossdraft, prefabricated crossdraft or downdraft/semi-downdraft). For near spray (bystander) samples, outdoor temperature >65 degrees F (18 degrees C) and shop size >5000 feet2 (465 m2) were significant determinants of exposure levels. For workplace background samples the shop annual income was the most important determinant. For sanding samples, the shop annual income and outdoor temperature >65 degrees F (18 degrees C) were the most significant determinants. Identification of these key exposure determinants will be useful in targeting exposure evaluation and control efforts to reduce isocyanate exposures.

Air Pollutants, Occupational↗
PubMed2004

Effect of high levels of intense sweetener intake in insulin dependent diabetics on the ratio of dietary sugar to fat: a case-control study.

OBJECTIVE: To examine the influence of intense sweetener consumption on nutrient intakes in insulin dependent diabetics compared to controls. DESIGN: Case-control food consumption survey. SETTING: Dietary data were collected from individuals in Ireland between 1998 and 1999. SUBJECTS: Diabetics were recruited through diabetic outpatient departments of St. James's Hospital Dublin. Controls were friends of the patients or staff/students of Trinity College and University College Dublin. Of the 171 diabetics contacted, 122 agreed to participate (70% response rate) and 119 completed the study. INTERVENTIONS: In all, 3-day food diaries were used to collect the food consumption data. MAIN OUTCOME MEASURES: Fat--sugar seesaw, intense sweetness. RESULTS: Patients had significantly higher % energy from starch, lower % energy from sugars and a high intake of fibre compared to controls. In both groups, there was an inverse relationship between % energy from fat and % en from sugar, with the diabetics at the lower level of sugar intake. A score of intense sweetness intakes was computed and across tertiles of this score, there were no significant effects on macronutrient intakes. CONCLUSION: The fat-sugar seesaw present in the diabetic group was at a lower level compared to the control group. A high intake of intense sweeteners does not have a detrimental effect on macronutrient and micronutrient intakes.

Adolescent↗
PubMed2003

Lung cancer. 4: chemotherapy for non-small cell lung cancer: the end of the beginning.

The development of chemotherapy for NSCLC over the last 20 years is reviewed, particularly with regard to its palliative effects. New "fourth generation" agents designed to inhibit specific biological pathways thought to be crucial to tumour growth give cause for optimism in the future treatment of NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

'Best supportive care' has had its day.

The term 'best supportive care' has been used since 1988 to describe the control arm in trials evaluating chemotherapy in advanced cancers. There are problems with this term. First, it implies that we more strenuously optimise these components of care in trials than in routine oncology practise, when there is no evidence that we do. Secondly, the name implies that it is effective, when usually it is not. Finally, 'best' suggests that we have reached a clear landmark of progress in non-chemotherapeutic palliation, when clearly we have not. 'Best supportive care' is an unhelpful and misleading term which should be avoided. In future trials, it should be replaced by 'standard palliative care ' with the type and frequency of key palliative interventions documented.

Humans↗
PubMed2001

Dynamic assessment of paranasal sinus ventilation using xenon-enhanced computed tomography.

Disease of the paranasal sinuses is a common and costly condition. Evaluation of the efficacy of either medical or surgical methods of treatment is limited by the lack of quantitative methods to characterize sinus ventilation, which may be an important determinant of the baseline physiological state of the sinuses. Xenon-enhanced computed tomography (Xe-CT) measurement of sinus ventilation provides a noninvasive method of quantifying maxillary sinus ventilation using the nonradioactive, radiodense gas Xe as a tracer. Study subjects breathed a mixture of Xe gas and oxygen through a close-fitting nasal mask during serial CT imaging of a single radiographic plane through the maxillary sinuses--a generally well-tolerated protocol. Analysis of the sinus density-time curves allowed calculation of first-order exponential time constants from which specific ventilation rates could be determined for individual sinuses. Previously developed data analysis techniques were used to assess the statistical significance of the data and determine confidence intervals, allowing examination of the effects of noise in the data, and to demonstrate areas for further study protocol refinement. We conclude that Xe-CT measurement of sinus ventilation is a potentially valuable noninvasive technique for the diagnostic imaging of the human maxillary sinus.

Humans↗
PubMed2001

A novel autosomal dominant distal myopathy with early respiratory failure: clinico-pathologic characteristics and exclusion of linkage to candidate genetic loci.

We describe a novel autosomal dominant myopathy presenting in mid-adult life with tibialis anterior weakness. We carried out a detailed clinical assessment of 24 individuals spanning three generations, documenting pathologic features of the muscles in 7 of the 11 affected individuals, including an autopsy study on one case. The second generation of affected individuals presented at an earlier age, and the disease progressed more rapidly than in the first generation. Lung function tests revealed progressive global respiratory muscle weakness detectable from the time of presentation, with preferential diaphragmatic involvement in some cases. Hip girdle and shoulder girdle weakness appeared later in the disease course. We observed a striking correlation between the clinical and pathological features. Clinically unaffected muscles had minimal pathologic change. Fiber splitting, eosinophilic inclusions, and vacuoles with basophilic rims were seen in moderately affected muscles, and fat and fibrous connective tissue replaced muscle fibers in the severely involved muscles. The inclusions were Congophilic and reacted with antibodies to desmin, beta-amyloid, and phosphorylated tau protein. The disease was not linked to any of the known loci associated with distal myopathies, confirming that the disorder in this family is both genetically and phenotypically distinct.

Adult↗
PubMed2000

Fine mapping of IGAD1 in IgA deficiency and common variable immunodeficiency: identification and characterization of haplotypes shared by affected members of 101 multiple-case families.

To limit the region containing a mutation predisposing to selective IgA deficiency (IgAD) and common variable immunodeficiency (CVID), 554 informative members of 101 multiple-case families were haplotyped at the IGAD1 candidate locus in the MHC. Microsatellite markers were placed onto the physical map of IGAD1 to establish their order and permit rapid haplotype analyses. Linkage analysis of this extended family set provided additional support for a strong susceptibility locus at IGAD1 with a maximum multipoint nonparametric linkage score in excess of 3. Although the transmission of maternal IGAD1 haplotypes from unaffected heterozygous parents to the affected offspring was in excess, this was not apparent in multiple-case families with a predominance of affected mothers, suggesting that this parental bias is influenced by the affection status of transmitting parents and supporting a maternal effect in disease susceptibility. Of 110 haplotypes shared by 258 affected family members, a single haplotype (H1) was found in 44 pairs of affected relatives, accounting for the majority of the IGAD1 contribution to the development of IgAD/CVID in our families. The H1 allelic variability was higher in the telomeric part of the class III region than in the distal part of the class II region in both single- and multiple-case families. Incomplete H1 haplotypes had most variant alleles in the telomeric part of the analyzed region in homozygous IgAD/CVID patients, whereas this was not observed in unaffected homozygotes. These data suggest that a telomeric part of the class II region or centromeric part of the class III region is the most likely location of IGAD1.

Alleles↗
PubMed2000

The pediatric trauma C-spine: is the 'odontoid' view necessary?

BACKGROUND/PURPOSE: The "odontoid view" is a difficult and often hazardous film to obtain in young children. The aim of this study was to determine if the transoral roentgenogram is necessary in the evaluation of the pediatric cervical spine. METHODS: A retrospective, multiinstitutional review was performed of all patients 16 years of age and under with documented cervical spine injury in a large metropolitan area during the past decade. Fifty-one children with cervical spine injury were identified from the medical records at 4 hospitals. RESULTS: The 0- to 8-year-old age group had a significantly higher incidence of upper (occiput to C3) cervical injury than the 9- to 16-year-old age group (67% v 39%; P < .05). In the 0- to 8-year-old group the initial lateral/anteroposterior radiograph made the diagnosis of cervical spine injury in 13 of 15 patients (87%), and in no patients was the transoral odontoid view used to make the diagnosis of cervical spine injury. In only 1 patient in the 9- to 16-year-old age group with a type III odontoid fracture was this view deemed useful. The overall mortality rate in this series was 7.8% with all deaths secondary to associated head injury. CONCLUSIONS: In the 0- to 8-year-old age group in whom the incidence of cervical spine injury is rare but frequently involves the upper cervical spine, the transoral odontoid roentgenogram may be of little value in the evaluation of the spine and should not be considered necessary in "clearing" the pediatric cervical spine. An alternative evaluation of these patients would include an initial lateral and AP radiograph, followed by computed tomography scan.

Cervical Vertebrae↗
PubMed1999

An analysis of the incremental value of retaining brand-level information in food consumption databases in estimating food additive intake.

In the Dietary and Nutritional Survey of British Adults (DNSBA) food consumption database, brand level intake data are recorded for 2197 subjects over 7 days. This study set out to examine the incremental value of such brand level data in food consumption studies to estimate additive intake. The food codes in the DNSBA database were re-arranged into 14 food categories within each of which were varying numbers of both sub-categories of foods and of brands. Intake of the 97.5th percentile for brands and sub-categories were compared with intakes at the 97.5th percentile of the appropriate food category. Taking > or = 60 consumers as the minimal sample size for which a 97.5th percentile statistic can be calculated, only 6% of the 1363 brands listed had sufficient data to work with. Of the 14 food categories, six had a sub-category with a 97.5th percentile in excess of that of the category but none exceeded 1.3 x 97.5th percentile intake of the category. Of the 85 brands for which there were > or = 60 consumers, only 11 had 97.5th percentile intakes in excess of that statistic for the relevant food category and none exceeded a multiple of 1.3 times the category 97.5th percentile intakes. Unless dietary surveys are very large and carried out for longer periods of time, there is little value in retaining food consumption data at brand level. If 1.3x the intake of an additive from a given food category at the 97.5th percentile does not exceed the ADI, no sub-category or brand appears to do so. This may provide a valuable technique in crude estimates of food additive intake.

Adolescent↗
PubMed1998

Characterization of 12 microsatellite loci of the human MHC in a panel of reference cell lines.

The human genome contains a large number of interspersed microsatellite repeats which exhibit a high degree of polymorphism and are inherited in a Mendelian fashion, making them extremely useful genetic markers. Several microsatellites have been described in the HLA region, but allele nomenclature, a set of broadly distributed controls, and typing methods have not been standardized, which has resulted in discrepant microsatellite data between laboratories. In this report we present a detailed protocol for genotyping microsatellites using a semi-automated fluorescence-based method. Twelve microsatellites within or near the major histocompatibility complex (MHC) were typed in the 10th International Histocompatibility Workshop homozygous typing cell lines (HTCs) and alleles were designated based on size. All loci were sequenced in two HTCs providing some information on the level of complexity of the repeat sequence. A comparison of allele size obtained by genotyping versus that obtained by direct sequencing showed minor discrepancies in some cases, but these were not unexpected given the technical differences in the methodologies. Fluorescence-based typing of microsatellites in the MHC described herein is highly efficient, accurate, and reproducible, and will allow comparison of results between laboratories.

Alleles↗
PubMed1998

Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens.

OBJECTIVE: To evaluate the effect of low to moderate occupational lead exposure on thyroid function we conducted a cross-sectional study of 151 male lead smelter workers. METHODS: Parameters of thyroid function were assessed in relation to both subacute and cumulative lead exposure over a 10-year employment period. Blood lead levels, obtained from plant surveillance records, were used to establish four ordinal levels of current and cumulative exposure (< 15, 15-24, 25-39, and > or =40 microg/dl). RESULTS: Mean values for the lowest as compared with the highest current exposure group were similar for thyroxine (T4: 6.8 versus 6.1 microg/dl), estimated free thyroxine (EFT4: 1.6 ng/dl in both groups), and thyroid-stimulating hormone (TSH: 1.8 versus 1.7 mIU/l); there was no evidence of a significant trend for diminished thyroid function associated with increasing current lead exposure. Similarly, no significant difference was observed for T4, EFT4, or TSH in relation to the 10-year cumulative exposure or for adjusted analyses controlling for potential confounders, including age and alcohol use. CONCLUSION: In contrast to studies observing thyroid dysfunction in the setting of high lead exposure and related clinical poisoning, our findings weigh against a significant physiologic effect on thyroid function at lower levels (< 60 microg/dl) of occupational lead exposure.

Adult↗