In search of the unknown primary.
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Carcinoma↗
Biomedical subjects
C Bradley
Publications and source records attributed to C Bradley.
Effect of acidified enteral feedings on gastric colonization in the critically ill patient.
OBJECTIVE: To evaluate the effect of acidified enteral nutritional formulas (feedings) on gastric colonization and pH in critically ill patients. DESIGN: Randomized, double-blind trial of three groups: a) regular feedings into the stomach; b) regular feedings into the duodenum; and c) acidified feedings into the stomach. Nasogastric aspirates for gastric pH and microbiological determinations were obtained daily for a mean of 5 days after feeding began. SETTING: ICU at a tertiary care hospital. PATIENTS: Thirty-one patients indicated to receive enteral feedings before day 4 in the ICU were randomized. Seven patients had their feedings discontinued because of intolerance, accidental extubation, or tolerance of oral supplementation. One patient received the wrong feedings and was dropped from the study. A total of 23 patients finished the study. They were mostly trauma (n = 15) or neurosurgical (n = 6) patients. The average age was 40 yrs (range 15 to 71). INTERVENTIONS: An enteral formula with a pH of 6.5 was used as the control feeding. Hydrochloric acid was added to the control feeding to titrate the pH to 3.5 and this acidified enteral formula was given to the experimental group. All patients received continuous enteral feedings via an 8-Fr feeding tube. MAIN RESULTS: Seven of eight patients receiving the acidified feedings were sterile (no microbial growth) on receiving feedings compared with five of 15 of those patients receiving regular feedings (p = .027). For those patients initially colonized, four of four patients receiving acidified feedings immediately became sterile and remained so. Only two of ten patients receiving regular feedings remained sterile (p = .021). The mean gastric pH of the acidified group was 3.2 compared with the group receiving regular feedings into the stomach (pH = 4.7) and the group receiving regular feedings into the duodenum (pH = 3.8) (p < .01). There was no evidence of gastrointestinal bleeding in any patient. CONCLUSIONS: Acidified enteral feedings are effective in eliminating and preventing gastric colonization in critically ill patients. Further investigation is needed to assess its effect on nosocomial infection rates.
Acidosis, Lactic↗
Down syndrome: molecular mapping of the congenital heart disease and duodenal stenosis.
Down syndrome (DS) is a major cause of congenital heart and gut disease and mental retardation. DS individuals also have characteristic facies, hands, and dermatoglyphics, in addition to abnormalities of the immune system, an increased risk of leukemia, and an Alzheimer-like dementia. Although their molecular basis is unknown, recent work on patients with DS and partial duplications of chromosome 21 has suggested small chromosomal regions located in band q22 that are likely to contain the genes for some of these features. We now extend these analyses to define molecular markers for the congenital heart disease, the duodenal stenosis, and an "overlap" region for the facial and some of the skeletal features. We report the clinical, cytogenetic, and molecular analysis of two patients. The first is DUP21JS, who carries both a partial duplication of chromosome 21, including the region 21q21.1-q22.13, or proximal q22.2, and DS features including duodenal stenosis. Using quantitative Southern blot dosage analysis and 15 DNA sequences unique to chromosome 21, we have defined the molecular extent of the duplication. This includes the region defined by DNA sequences for APP (amyloid precursor protein), SOD1 (CuZn superoxide dismutase), D21S47, SF57, D21S17, D21S55, D21S3, and D21S15 and excludes the regions defined by DNA sequences for D21S16, D21S46, D21S1, D21S19, BCE I (breast cancer estrogen-inducible gene), D21S39, and D21S44. Using similar techniques, we have also defined the region duplicated in the second case occurring in a family carrying a translocation associated with DS and congenital heart disease. This region includes DNA sequences for D21S55 and D21S3 and excludes DNA sequences for D21S47 and D21S17.(ABSTRACT TRUNCATED AT 250 WORDS)
Blotting, Southern↗
Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction.
Only small numbers of cells from solid tumours are needed for haematogenous metastasis. Detection is difficult because existing techniques are not sensitive enough. We have used reverse transcriptase to make complementary DNA from peripheral blood messenger RNA, and the polymerase chain reaction (PCR) to amplify cDNA specific for a gene actively transcribed only in the tumour tissue type. We prepared cDNA from peripheral blood of seven patients with malignant melanoma, four patients with other metastatic cancers, and four healthy subjects, as well as from several melanoma-derived cell lines. PCR was used to amplify the gene for tyrosinase, a tissue-specific gene in melanocytes. Since normal melanocytes are not thought to circulate in peripheral blood, detection of tyrosinase transcription in peripheral blood should indicate the presence of circulating cancer cells. The method was highly sensitive and could detect a single melanoma cell from a cell line in 2 ml normal blood. Blood samples from four of the seven patients with malignant melanoma gave positive results, whereas all eight control subjects gave negative results. This method does not depend on the characterisation of cancer-specific genetic abnormalities and can be applied to any cancer for which tissue-specific genes can be identified, including epithelial cancers. It could prove useful in the diagnosis of primary or metastatic cancers, in assessing prognosis, and in detecting residual disease after treatment.
Amino Acid Sequence↗
Rapid purification and characterisation of HIV-1 reverse transcriptase and RNaseH engineered to incorporate a C-terminal tripeptide alpha-tubulin epitope.
The C-termini of p66 and p51 forms of HIV-1 reverse transcriptase have been engineered to contain a Glu-Glu-Phe sequence recognized by a monoclonal antibody to alpha-tubulin, YL1/2. Mutated RTs were purified in a single step using peptide elution from columns of immobilized YL1/2. The known sequence requirements of the YL1/2 epitope are consistent with protein eluting from the column with an intact C-terminus. Kinetic parameters of these mutated RTs are essentially unchanged from wild-type enzyme. The p15 RNaseH domain has been purified using this method and shown to have low enzyme activity compared to the parental p66 subunit.
Amino Acid Sequence↗
Comparison of functional activities between IgG1 and IgM class-switched human monoclonal antibodies reactive with group B streptococci or Escherichia coli K1.
The influence of valence and heavy chain on antibody activity was investigated using transfectoma-derived, class-switched IgG1 and IgM human monoclonal antibodies (MAbs) reactive with the bacterial pathogens Escherichia coli K1 and group B Streptococcus species. IgG-IgM pairs were compared in vitro for antigen binding and opsonic activities and in vivo for protective efficacy in neonatal rats. For the anti-E. coli pair, the IgM MAb was 1000-fold more potent in all assay formats. Importantly, the 50% protection dose (PD50) of the IgM MAb was 10-20 ng/rat, while 100 micrograms of the IgG MAb was only minimally protective. For the group B streptococcal MAbs, the IgM was 100- and 4500-fold more potent in binding and opsonization assays, respectively. However, while 20 micrograms of IgM protected neonatal rats, 100 micrograms of IgG MAb was partly protective. These experiments demonstrate the utility of recombinant DNA technology for creating a panel of antibodies that may aid in selecting potential immunotherapeutic candidates.
Animals↗
Audit fever: a gentle warning.
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Community Health Services↗
A new point mutation in the 3,5,3'-triiodothyronine-binding domain of the c-erbA beta thyroid hormone receptor is tightly linked to generalized thyroid hormone resistance.
Two different mutations in the c-erbA beta thyroid hormone receptor have recently been reported as genetic abnormalities responsible for the syndrome of generalized thyroid hormone resistance (GTHR). We have now found in a third kindred, D, in which GTHR is inherited as a dominant disease, a new point mutation in the T3-binding domain of c-erbA beta. A guanine to cytosine base substitution at nucleotide position 1305, which altered codon-335 from glutamine (CAG) to histidine (CAC), was found in one allele of 10 affected members and was not found in 6 unaffected members. This C-1305 sequence was not present in 106 random alleles, indicating that it was a mutation in c-erbA beta, and it was tightly linked to GTHR in kindred D, with a maximum logarithm of the odds score of 4.19 at a recombination fraction of 0. The tight linkage result confirms that GTHR maps to the c-erbA beta locus in multiple kindreds. In view of the tight linkage between the C-1305 mutation and GTHR, and that this mutation is a nonconservative alteration in a crucial region of the T3-binding domain, it is probably the genetic defect in kindred D responsible for GTHR. The kindred D receptor appears to result in a different phenotype of tissue resistance compared to the previously reported kindred. A receptor with a mutation in the carboxy-terminus of c-erbA beta.
Base Sequence↗
Randomized trial comparing continuous subcutaneous insulin infusion and conventional insulin therapy in type II diabetic patients poorly controlled with sulfonylureas.
OBJECTIVE: To compare the effects of continuous subcutaneous insulin infusion (CSII) and conventional insulin therapy (CIT) in patients with poorly controlled sulfonylurea-treated diabetes mellitus. RESEARCH DESIGN AND METHODS: Twenty-five patients aged 40-65 yr and poorly controlled with sulfonylureas and without severe diabetic complications comprised the study group. Five patients left the study (3 achieved satisfactory glycemic control without insulin, 1 defaulted, 1 developed ketonuria). Ten patients were treated with CSII and 10 with CIT. Outpatient treatment consisted of CIT (twice-daily injections of regular and NPH insulin) or CSII (basal infusion and prandial boluses of regular insulin). RESULTS: Glycosylated hemoglobin improved with both methods of insulin delivery (P less than 0.01), but 8 of 10 CSII-treated patients achieved satisfactory glycemic control (HbA1 less than 50 mmol hydroxymethylfurfural/mol Hb), whereas only 3 of 10 CIT-treated patients achieved this (P less than 0.05). Weight gain, insulin dosage, and prevalence of hypoglycemia were similar in the two groups. Retinal deterioration occurred in one CSII-treated patient and three CIT-treated patients, but there were no episodes of infusion site infection or metabolic decompensation. Patients' satisfaction with treatment improved during insulin therapy (P less than 0.02), and significant changes in beliefs about diabetes and its treatment were observed in CSII-treated patients (P less than 0.05). CONCLUSIONS: Glycemic control improved with both methods of insulin treated patients achieved satisfactory glycemic control (HbA1 less than 50 mmol hydroxymethylfurfural/mol Hb), whereas only 3 of 10 CIT-treated patients achieved this CSII. Patients' satisfaction with treatment improved during insulin therapy.
Adult↗
Major chest wall resection for recurrent breast carcinoma.
Local recurrence of breast cancer is a relatively common entity. Occasionally, the management of such recurrences necessitates full-thickness chest wall resection. Although the chance for cure in such circumstances is small, achieving local control remains a desirable goal to maintain comfort and hygiene. This study evaluates the utility and morbidity of full-thickness chest wall resection in the control of symptomatic local recurrence of breast carcinoma. Twelve patients, undergoing such resections, were identified from hospital records. The resections included an average of three ribs (range, two to five) and, in seven cases, part or all of the sternum. A variety of rigid and soft tissue chest wall reconstructive techniques were utilized. Of the 11 patients available for follow-up, ten reported good overall function postoperatively. There were no postoperative deaths and only one patient developed a major complication requiring prolonged hospital stay. The patients spent an average of 6.6 hours in surgery, 14.6 hours intubated, and 20 days in the hospital. There were ten patients available for long-term follow-up. At the time of this study, 70 per cent were still alive, with or without disease, with a mean survival of 27 months (range, 3-71 months). Forty per cent were alive, disease-free, with a mean survival of 36 months (range, 3-71 months). This series demonstrates low morbidity, improved quality of life, and the possibility of long-term, disease-free survival after full-thickness chest wall resection for recurrent breast carcinoma.
Adult↗
Hepatic zinc in hemochromatosis.
Since an intestinal absorptive interaction between iron and zinc has been described in animals and humans, the possibility of increased accumulation of zinc as well as iron in the liver was studied in patients with hereditary hemochromatosis. Hepatic zinc was determined by atomic absorption spectrophotometry in liver biopsy specimens from 21 homozygotes for hemochromatosis, 21 normal liver samples from autopsies, and 15 cases of cirrhosis unrelated to iron overload. Mean hepatic zinc concentrations in the three groups were compared by one-way analysis of variance. Hemochromatosis patients had hepatic iron determinations by atomic absorption spectrophotometry, and iron absorption studies using 59Fe and total body counting had been previously documented in 18 of the 21 hemochromatosis patients. The mean hepatic zinc was significantly increased at 25.9 +/- 26.7 mumol/g (dry weight) in the hemochromatosis patients, as compared to 4.99 +/- 1.51 mumol/g in the control patients (p less than 0.05), and 2.13 +/- 1.13 mumol/g in the cirrhosis patients without iron overload (p less than 0.05). Hepatic zinc concentration was elevated in hemochromatosis patients who had either normal histology, fibrosis, and cirrhosis. Hepatic zinc concentration was not directly related to patient age, hepatic iron concentration, or iron absorption. In conclusion, hepatic zinc was increased approximately fivefold in patients with hemochromatosis. This finding suggests the concomitant hepatic accumulation of zinc as well as iron in this disorder, possibly by means of increased intestinal absorption of zinc and hepatic sequestration.
Adult↗
Relationship between the pharmacokinetics and toxicity of mitozolomide.
The cytotoxic drug mitozolomide has been found to cause unpredictably severe thrombocytopenia during phase I and II clinical trials. In an attempt to relate dose and pharmacokinetic parameters to toxicity, we measured plasma concentrations of mitozolomide in 14 patients with a range of malignancies. There were significant correlations (Spearman rank correlation test) between drug clearance and AUC and white blood cell nadir. The pharmacokinetic and toxicity data were not normally distributed; therefore, it was not possible to construct predictive nomograms for toxicity based on linear regression analysis.
Adult↗
Virucidal activity of disinfectants: studies with the poliovirus.
The activity of various disinfectants against poliovirus (Sabin 1 an) was assessed using surface and suspension tests. The surface test showed that 2% glutaraldehyde and high concentrations of hypochlorites (9200 ppm avCl2) were effective (i.e. greater than or equal to 4 log10 reduction) against a dried virus suspension in 1 min. Diluted aldehydes ('Sporicidin' and 'Gigasept'), lower hypochlorite concentrations (1000 ppm avCl2) and peroxides (3%) were less effective while 70% ethanol showed variable results; 70% isopropanol was ineffective in 10 min. In the suspension tests hydrogen peroxide (3% and 6%) and 70% ethanol were ineffective in 1 min.
Disinfectants↗
Mycobacterium chelonei isolation from broncho-alveolar lavage fluid and its practical implications.
Mycobacterium chelonei was isolated from the broncho-alveolar lavage fluid of seven patients on eight occasions over a 6-month period. The same bacterium was identified in the hospital water supply. Despite the use of a recommended disinfection procedure, it proved impossible to eradicate the organism until the bronchoscopes were treated with ethylene oxide and the use of tap water in rinsing was abandoned.
Aged↗
Growth of mammalian cells on carbon-coated plastic substrata.
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Animals↗
Health belief scales developed specifically for people with tablet-treated type 2 diabetes.
The design and development of scales to measure diabetes-specific health beliefs of patients treated with oral hypoglycaemic agents and diet are described. The scales, which were developed from the responses of 187 tablet-treated patients, measure perceived Benefits of, and Barriers to Treatment, and perceived Severity of, and Vulnerability to Complications of diabetes and other disorders unrelated to diabetes. Cronbach's alpha indicated that each scale was internally reliable (alpha = 0.67 to 0.89) and construct validity was indicated by expected correlations between the scales and other variables including measures of blood glucose control, body weight, and psychological well-being. Thus, patients who were overweight and/or had higher glycosylated haemoglobin (HbA1) levels perceived their treatment to be less 'Cost-effective' (Benefits less Barriers), rated Complications as being more severe, and reported greater Vulnerability for themselves and the 'average person' with diabetes to these Complications (p less than 0.05 to p less than 0.01). Furthermore, respondents with higher Depression and Anxiety scores and lower Positive Well-being and Treatment Satisfaction scores reported greater Vulnerability to Complications for themselves and the 'average person', and also felt that their treatment was less 'Cost-effective' (p less than 0.01 to p less than 0.001). The measures are likely to be particularly useful in studies which assess the efficacy of interventions in modifying health beliefs with a view to achieving desired behaviours. They may also be useful as an instrument of audit if indicators about the suitability of possible interventions are sought.
Adult↗
Measures of psychological well-being and treatment satisfaction developed from the responses of people with tablet-treated diabetes.
Psychological outcome measures of Well-being and Treatment Satisfaction have been designed and developed for people with tablet-treated Type 2 diabetes. The Well-being scale includes three six-item sub-scales to measure Depression, Anxiety, and Positive Well-being. A prime consideration when selecting items for the psychological well-being measures was to minimize the confounding of diabetic symptomatology with the somatic symptoms of depression and anxiety. Cronbach's alpha indicated that each of the Well-being sub-scales and the Treatment Satisfaction scale was internally reliable (alphas ranged from 0.70 to 0.88) and evidence for construct validity was provided by predicted associations with other variables collected at the time of the study. For example, lower Well-being scores were associated with being overweight (Depression: p less than 0.05; Anxiety: p less than 0.001) while greater Satisfaction with Treatment was associated with lower HbA1 levels (p less than 0.001) and lower percent ideal body weight (p less than 0.01). These scales should prove particularly useful where measures of quality of life are required to complement metabolic variables when evaluating new treatments, education programmes, and other interventions, or in the routine auditing of established methods of treatment.
Adult↗
Multifocal central nervous system lesions and retropharyngeal lymphadenopathy on magnetic resonance imaging: an association that suggested progressive multifocal leukoencephalopathy in a patient with acute aphasia.
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Acquired Immunodeficiency Syndrome↗