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Biomedical subjects

P Clarke

Publications and source records attributed to P Clarke.

At least 127 records · Page 7Linked to original sources

An investigation into the effect of protective devices on the dose to radiosensitive organs in the head and neck.

A series of experiments were performed to determine the dose reduction afforded to radiosensitive organs in the head and neck by various protective devices. These included spectacles with plastic, standard glass, photochromic and lead-glass lenses, a thyroid collar and a lead-acrylic face mask. The measurements were performed using an anthropomorphic phantom loaded with lithium fluoride thermoluminescent dosemeters, in conditions realistic of clinical practice. Irradiations were performed using scattered radiation produced by a pelvic phantom, for X-ray beams generated at 80 kVp and 110 KVp. It was found that the reduction in dose to the lens of the eye ranged between 0% and 97%, whilst the dose to the thyroid and oesophagus was reduced by between 76% and 97%, and was dependent on the protective device and tube potential employed. A reduction in brain dose of up to 81% was also measured, for the lead-acrylic face mask. Also presented is the ratio of organ dose to dose to the bridge of the nose for thyroid, oesophagus, brain and sinuses, as measured for the case of no head or neck protection.

Brain↗

A prospective evaluation of the effect of tumor cell DNA content on recurrence in colorectal cancer.

Tumor cell DNA (ploidy) content was measured prospectively in samples from 320 patients resected for colorectal cancer with a minimum follow-up time of 2 years. All patients were followed and those with recurrence were investigated carefully. There was no correlation between tumors with an abnormal cellular DNA content (aneuploid or tetraploid) and patient age, sex, tumor site, pathologic stage, or histologic grade. In 236 patients who underwent potentially curative operations, 75 (32%) had local and/or distant recurrence. The recurrence rate was significantly higher (test statistic, 4.3; P = 0.04) for those patients with aneuploid tumors (52 of 142, 37%) compared with those with diploid tumors (23 of 94, 24%). The subgroups of patients where ploidy exerted an effect were in patients with Stage B tumors or mobile tumors and in patients over 65 years of age. Further analysis showed that there was a twofold increase in local recurrence and a threefold increase in distant recurrence in patients with aneuploid tumors, but no excess of patients who had both local and distant recurrence. Measurement of DNA ploidy can identify a group of patients undergoing curative surgery for colorectal cancer at high risk for recurrence. In combination with clinicopathologic factors, DNA ploidy may be useful in analyzing the results of trials and in planning adjuvant therapy.

Aged↗

Mutagenesis occurring following infection with herpes simplex virus does not require virus replication.

Infection of eukaryotic cells in culture with herpes simplex virus type-1 (HSV-1) or HSV-2 increased the mutation frequency of the supF gene carried on the shuttle vector pZ189 by around sixfold. The increase was apparent 2 hr postinfection and reached a peak after 8 hr. To investigate this mutagenesis, plasmids pCKRR1 and pCKRR2 were constructed to express the large and small subunits, respectively, of HSV-2 ribonucleotide reductase (RR) under the control of the inducible mouse metallothionein promoter. Expression from these plasmids, either singly or together, had no effect on the mutation frequency of pZ189 under conditions when virus RR activity was detected. The HSV-1 temperature sensitive (ts) mutant viruses ts 1207 and ts 1222, which have ts lesions in the genes encoding R1 and R2, respectively, were as mutagenic as wild-type HSV-1 at both the permissive and nonpermissive temperatures. These results indicate that expression of HSV RR is not mutagenic in this system. Experiments using other HSV-1 mutants and ultraviolet-inactivated virus localized the cause of the increased mutagenic frequency either to a component of the incoming virion or to an effect exerted by the virus DNA itself. The present study confirms previous reports that infection with HSV exerts a mutagenic effect. Further, virus replication and gene expression were not required for the mutagenic effect studied here. This may have implications for a role of HSV in cellular transformation, as a nonproductive infection could mutagenize cellular genes.

Cell Line↗

Characterization of the human and rat myoadenylate deaminase genes.

AMP deaminase is an ubiquitous enzyme in eukaryotic cells, and tissue-specific isoforms are produced in mammals by differential expression of the two genes which encode this enzyme activity as well as by alternative splicing of the primary transcript of one of these genes. Deficiency of this enzyme activity is one of the most common causes of metabolic myopathy in man. To provide a framework for understanding the molecular basis of this inherited disorder and the mechanisms responsible for regulating the expression of this enzyme activity, both the human and rat muscle-specific genes for AMP deaminase have been cloned and partially sequenced. Comparison of the two genes shows a high degree of conservation of sequence and structural organization. The two genes share the following characteristics: 1) both are approximately 20 kilobases in size, have identical exon/intron boundaries, and exhibit similar intron/exon structural organization; 2) the transcription start site is located at the same position in both genes, and comparison of 5'-flanking sequences reveals four highly conserved domains that together contain the information necessary for muscle-specific expression of a receptor cDNA; 3) coding sequences are 88% identical and the 5'-untranslated regions are 67% identical; 4) both genes have extremely short 3'-untranslated regions (13-17 nucleotides); 5) highly conserved intervening sequences of several hundred nucleotides surround most exon/intron boundaries. In situ hybridization and analysis of human-mouse somatic cell hybrids have localized the human gene (designated AMPD1) to chromosome 1 in the region p13-p21. The implications of these structural properties for identifying functional domains in the AMP deaminase peptide, regulation of expression of this gene, and inheritance of AMP deaminase deficiency are discussed.

AMP Deaminase↗

The influence of tumour cell DNA content on survival in colorectal cancer: a detailed analysis.

We have investigated the influence of tumour cell DNA content (ploidy) on survival of 416 patients undergoing excisional surgery for colorectal cancer. Two hundred and eleven (51%) tumours had an abnormal DNA content (aneuploid or tetraploid). There was no correlation between ploidy status, sex, age and pathological stage, histological grade, tumour site, local tumour extension or assessment of curability. Patients with tumours with an abnormal DNA content had a poorer survival 68/211 (32%) than patients with near normal (diploid) DNA content 88/205 (43%) (test statistic 5.0, P = 0.02). The patient subgroups in which DNA content exerted an influence on survival were: stage B tumours (P = 0.0058), moderately differentiated tumours (P = 0.004), rectal tumours (P = 0.02), and mobile tumours (P = 0.02). Multivariant analysis showed that pathological stage, local tumour extension and DNA ploidy were all independent prognostic indicators whereas histological grade, tumour site and assessment of 'curability' were not. The influence of pathological stage, however, was much greater than that of local tumor extension or DNA ploidy. Tumour cell DNA content together with pathological stage and local tumour extension may be used in a prognostic index and may be important in planning adjuvant therapy.

Adult↗

Water birth.

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Adult↗

Group education for obese patients with type 2 diabetes: greater success at less cost.

It has been suggested that much effort expended in teaching diabetic diets is ineffective and wasteful. We have tested a different system by randomly allocating 75 newly diagnosed obese Type 2 diabetic patients to usual 'unstructured' clinic care or to group education by diabetes specialist nurses and a dietitian. Patients allocated to group education attended five 90-min group sessions during the first 6 months. Six months after diagnosis they had lost more weight (median (95% Cl), 7 (5.5-9) vs 2(1-5)kg, p less than 0.002) and were better controlled (HbA1:7.5 (7.0-8.1) vs 9.5 (8.7-10.4)%, p less than 0.001) than those randomized to the usual clinic system. At 1 year (after no further visits) the difference in weight loss was less (5.5 (4-6.5) vs 3 (2-4) kg, p less than 0.05) and diabetic control was similar (HbA1:9.0(8.2-9.8) vs 9.9(8.9-10.9)%. At 1 year only 14(39%) of the education group and 9(23%) of those attending the clinic had a fasting blood glucose less than 7.0 mmol l-1.

Blood Glucose↗

A randomised prospective comparison of cefotaxime versus netilmicin/penicillin for treatment of suspected neonatal sepsis.

In an open prospective study performed in 2 neonatal units, infants with suspected neonatal sepsis (SNS) of unknown microbial cause were randomly allocated to receive treatment with either cefotaxime (CTX) or netilmicin plus penicillin (N + P). 236 patients were entered into the trial, of whom 222 were evaluable. The number of 'definitely' and 'probably' infected babies was similar in both groups. There was no difference in clinical outcome between patients in the 2 treatment groups and no side effects were recorded for either of the antibiotic regimens. Antibiotic sensitivity testing of bacterial isolates from peripheral sites showed almost universal sensitivity of potential pathogens to both antibiotic regimens at the start of treatment in all infants. Thereafter, organisms resistant to CTX were isolated from patients in both treatment groups, possibly reflecting the antibiotic sensitivity profile of the colonising bacteria in both neonatal units. The results of this study indicate that either CTX or N + P are suitable, in our units, for the 'blind' treatment of early SNS. In units where listerial infections are prevalent, specific cover should be added to CTX. For SNS developing after admission, the choice of antibiotics will depend upon the background antibiotic sensitivity profile of the colonising bacteria.

Bacterial Infections↗

Starting insulin treatment as an outpatient. Report of 100 consecutive patients followed up for at least one year.

Most textbooks advise that newly diagnosed insulin-dependent diabetics be admitted to the hospital. Nevertheless, if they are not acutely ill, we start insulin treatment on an outpatient basis. We report herein the logistics, efficacy, and safety of our system. Over two years, 115 newly diagnosed insulin-dependent diabetics were seen in our hospital. Fifteen (66% of them ketoacidotic) were admitted. The other 100 were treated as outpatients by a nurse specialist with a starting dosage of 6 to 10 units of intermediate-acting insulin twice daily. Hemoglobin A1 concentration at diagnosis was 15.2% +/- 2.7% (mean +/- SD); at six months, 10.9% +/- 2.9%; and at one year, 10.6% +/- 2.8%. Only three outpatient starters were hospitalized in the first year, one for hypoglycemia and two with respiratory tract infections. Our findings suggest that outpatient stabilization is both safe and cost-effective.

Adolescent↗