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Biomedical subjects

P D Murphy

Publications and source records attributed to P D Murphy.

At least 19 recordsLinked to original sources

Serosal imprint cytology in colonic cancer: a simple staging technique.

Accurate staging of colonic cancer is essential in defining the rational use of adjuvant treatments. Recent studies have shown that prognostic accuracy can be significantly improved by recognition of primary tumour extension to the free serosal surface. This study compares the technical results of serosal imprint cytology with the results of histology in assessing serosal involvement. When analysed in terms of the modified Dukes' staging the results of cytology imprints taken from the peritoneum overlying the colonic primary were positive for tumour cells in 4/13 Dukes' B, 7/14 Dukes' C, and 5/9 metastatic cancers. Imprint cytology was positive in 6/7 Dukes' B and C cases with histological serosal invasion and was suspicious in the remaining case. However, a further 5/20 cases without identified invasion on routine histology also had positive cytology. Imprint cytology is an adjunct to routine histology which is easily performed and allows more precise staging of serosal involvement in Dukes' B and C colonic cancers. Final evaluation of this technique requires long-term follow-up of patients.

Colon

Molecular confirmation of alpha 1-antitrypsin genotypes in newborn dried blood specimens.

Deficiency of alpha 1-antitrypsin (alpha 1AT), a common hereditary disorder of Caucasians, is associated with an increased risk for early-onset chronic obstructive pulmonary disease and childhood liver dysfunction. The two most common deficiency variants, PiS and PiS, are both single base-pair substitutions causing amino acid modifications, although neither mutation creates or destroys a naturally occurring restriction site. Dried blood specimens (DBS) submitted to the New York State Department of Health for mandated newborn screening tests were tested for alpha 1AT activity using a fluorometric elastase inhibition assay. A second DBS from specimens determined to be alpha 1AT deficient was phenotyped on an agarose isoelectric focusing gel. Genotypic confirmation was performed by amplifying, directly from a DBS, the regions of the DNA containing the S and Z mutation. The Z mutation was analyzed with a modified primer designed to create an artificial restriction site in the normal allele. TaqI digestion produces two bands, a 157- and a 22-bp fragment. The single base substitution in PiS individuals eliminates this TaqI restriction site, thus showing the same 179-bp fragment before and after digestion. A primer mismatch placed close to the S mutation creates a restriction site in the normal allele, producing a 100-bp product after TaqI digestion. The restriction site is abolished in individuals that carry the S mutation, with a 121-bp product observed before and after digestion. Of 11,081 specimens screened, 3 PiS neonates, all Caucasian, were detected by these methodologies for an estimated incidence of 1:2019 in the Caucasian or 1:3694 in the general population in New York State.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

Free peritoneal tumour cell identification in patients with gastric and colorectal cancer.

The finding of free tumour cells within the peritoneum at the time of laparotomy for gastrointestinal cancer is an important indicator of prognosis and may help select treatment. The aim of this study was to improve the methods whereby these cells could be retrieved and identified. Free peritoneal cancer cells were found in 6 out of 18 gastric cancer patients. All 6 patients had tumour invasion through to the serosa and subsequently died of tumour recurrence. None of the 18 Dukes' B and C colorectal cancer patients had free peritoneal cancer cells. Only 2 of a further 5 patients with extensive colorectal tumour spread had positive cytologies. The conventional mucin stain Periodic Acid Schiff (after diastase digestion) and the monoclonal antibody stain B72.3 were the most useful in identifying free peritoneal cancer cells. Peritoneal brushings did not offer any advantages over conventional peritoneal washings in the retrieval of free tumour cells.

Adult

Ten-year review of treatment of the undescended testis in the west of Ireland.

Advances continue to be made in the treatment of the undescended testis, and treatment recommendations are continually changing. We reviewed 543 patients admitted for treatment of undescended testes in the 10-year period 1977 to 1986. The side and position of the testis were recorded, the patient's age at operation and the procedure carried out. The presence of an associated inguinal hernia was noted. The necessity for reoperation was recorded and predisposing factors sought. We found the mean age at operation to be 9.5 years and this decreased significantly over the study period. Dartos pouch orchiopexy was the commonest operation (69%). No significant link was found between the procedure performed or the presence of a hernia and the need for further procedures; 2.7% of patients required such further procedures. A coherent classification of position is lacking for abnormally descended testes. We report a classification which we used to tackle this situation.

Adolescent

Adenocarcinoma of the gallbladder--a 5 year review of outcome in Newcastle upon Tyne.

Patients presenting with adenocarcinoma of the gallbladder within Newcastle upon Tyne over a 5 year period (1980-1985) were reviewed retrospectively. The mean age of patients on diagnosis was 74 years. Of the 29 patients diagnosed, two were detected after routine cholecystectomy. Laparotomy was performed in 21 patients (72%) of which only 14 patients had a cholecystectomy performed. Mean survival after surgery was 6.6 months with only one patient alive after 5 years. Metastatic disease was present in 72% of patients. The poor prognosis of carcinoma of the gallbladder reflects its late diagnosis and early metastasis to distant sites. Improvement in survival will depend upon early detection of in situ lesions and identification of at risk patients.

Adenocarcinoma

Molecular markers of fragile X: clinical aspects of carrier detection and prenatal diagnosis.

In our families, a determination of carrier or affected status was made in more than 75% of cases using a standard panel of five marker systems: three proximal (F9, DXS105, DXS98) and two distal (F8, DXS52). Five additional systems, three proximal (DXS10, DXS51, DXS102) and two distal (DXS15, DXS33), were used in cases resistant to analysis with the standard panel. In 60% of cases, flanking markers were identified (proximal and distal). Utilizing the complete panel, only 5% of cases did not have any informative markers identified. In order to facilitate the appropriate application of molecular methods, several simple rules should be followed by the genetic service provider when dealing with fra(X) families: 1. Cytogenetic prescreening of females may be helpful. Only negative or ambiguous fra(X) expression levels justify the labor-intensive DNA-based family studies. 2. At present, DNA-based studies are the only way to ascertain male carrier status. 3. Every effort should be made to perform DNA-based studies under maternal phase-known conditions. 4. Information should be collected and pedigrees prepared for both sets of maternal grandparents. 5. Fathers of female consultands should be directly DNA-typed to rule out non-paternity. 6. Genetic counseling should be conservative, i.e. the "worst" scenario presented to these families, in order to avoid underestimating the risk of transmission to the next generation.

Cells, Cultured

Effect of the menstrual cycle on gastric emptying.

Gastric emptying of both solid- and liquid-phase markers was assessed in 7 normally-menstruating women who had undergone bilateral Fallopian tube ligations. The women were studied once during the follicular phase of their menstrual cycle and again during the luteal phase. Emptying of the liquid-phase marker was not significantly different during the two phases of the menstrual cycle. However, emptying of the solid-phase marker was significantly slower during the luteal phase of the cycle as compared to the follicular phase. This impairment of gastric emptying of solid was correlated with elevated serum levels of progesterone. This study demonstrates that the rate of gastric emptying of solids may vary with the phases of the menstrual cycle.

Adult

Esophageal motor abnormalities in gastroesophageal reflux and the effects of fundoplication.

Recordings of esophageal manometry obtained from 18 healthy control subjects and 32 patients with gastroesophageal reflux disease both before and after fundoplication were assessed. Preoperatively, the patients had a mean lower esophageal sphincter pressure at rest that was significantly lower (p less than 0.001) than that observed in the control group. The amplitude of peristaltic contractions, elicited by wet swallows, varied along the length of the esophagus. In patients with gastroesophageal reflux disease, the mean amplitudes recorded from the upper, middle, and lower esophagus were significantly lower (p less than 0.001) than those recorded from control subjects. No significant differences were observed between those patients with (53%) and without preoperative endoscopic evidence of esophagitis. After antireflux surgery (modified Nissen fundoplication), the mean amplitude of peristaltic contractions increased significantly (p less than 0.001) at all levels of the esophagus and were not significantly different from control values. This study describes motor abnormalities in the body of the esophagus associated with gastroesophageal reflux disease. These may arise secondary to gastroesophageal reflux inasmuch as they disappear after fundoplication.

Adolescent

Isolation and regional mapping of random X sequences from distal human X chromosome.

Chromosome-mediated gene transfer (CMGT) lines were shown to be convenient donors of genomic sequences from specific regions of the genome adjacent to selectable markers. Two libraries were prepared from CMGT lines carrying sequences spanning the long arm of the human X chromosome from HPRT (Xq26) to G6PD (Xq28). A series of 22 CMGT lines sharing the same selectable marker (HPRT) were used in conjunction with five standard translocation hybrids to provide fine-resolution regional mapping of the nonrepetitive X specific probes isolated from the libraries. The order of three human recombinant sequences with respect to known X-linked markers is: PGK (Xq13), 05-02 (DXS78); HPRT (Xq26), 07-03 (DXS79); surface antigen S11 (Xq27), 07-14 (DXS80); and G6PD (Xq28).

Animals