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Biomedical subjects

P D Chapman

Publications and source records attributed to P D Chapman.

At least 19 recordsLinked to original sources
PubMed2001

Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis.

BACKGROUND: It has yet to be established whether proliferative activity in the macroscopically normal colonic mucosa is causally correlated with neoplastic risk. Measurement of proliferative activity in human subjects is of necessity usually undertaken using indirect methods with inherent limitations, and relatively little has been published on the effect of normal biological variables on such indices. AIMS: To establish the validity of mitosis counts following whole crypt microdissection as an index of the crypt cell proliferative state (CCPS) and to examine the effect of normal biological variables (age, sex, and colonic site) and colonic neoplasia on the mitotic index in macroscopically normal human colon. SUBJECTS: Mucosal samples were obtained at colectomy or colonoscopy from 107 individuals (24 controls, 23 sporadic adenoma patients, 31 sporadic carcinoma patients, and 29 patients with familial adenomatous polyposis (FAP)). METHODS: Mucosal specimens were hydrated, hydrolysed, and small groups of crypts separated from the main specimen under a dissecting microscope. The total number of mitoses/crypt were counted by one observer for each of 10 complete crypts. RESULTS: Validation work established that whole crypt mitoses counts were reliable and reproducible. There was no relation between age and mean mitoses/crypt (Pearson correlation coefficient -0.1). The CCPS count was higher for males than for females (difference in means 2.8 (95% confidence interval 0.80-4.66)) among controls but there was no gender difference in the three disease groups. For all disease groups and controls, the crypt mitotic count showed a significant linear increase (p=0.004) from the rectum to the caecum. Biopsies from within 5 cm of the macroscopic margin of a carcinoma (near) gave a mean mitosis count of 12.6 while those from more than 10 cm (far) were lower but not significantly so (p=0.12) with a count of 9.0. The mean mitoses/crypt were similar for the controls and adenomas (5.6 and 4.7, respectively) but greater for the cancers and especially for FAP (8.3 and 14.2, respectively). Statistical analysis confirmed that there were significant differences (p<0.05) between controls and all disease groups together, between sporadic disease and FAP, and between adenoma and carcinoma subjects at each of the four colonic sites. Post hoc comparison by t test showed significantly greater CCPS for FAP compared with controls (p<0.001) and for sporadic cancer versus controls (p=0.04). CONCLUSIONS: Whole crypt microdissection and mitosis counting is a reliable, reproducible, and robust technique for assessing CCPS in the human colon. CCPS is unaffected by age but increases from the distal to the proximal colon. CCPS is increased if a sporadic cancer is present and markedly increased in FAP. However, the precise relation of an increased CCPS to the neoplastic process remains uncertain.

Adenoma↗
PubMed2001

Susceptibility markers in colorectal cancer.

Many susceptibility factors contribute to an individual's risk of developing colorectal cancer. Family history of colorectal cancer (particularly with early age of onset), maleness and increasing age are all factors associated with increasing risk. About three quarters of colorectal cancers are thought to be due to somatic mutations, and both high- and low-penetrance predisposing genes contribute to the remaining quarter of cases. Many of the highly penetrant dominant genes are known, but others remain to be identified. Describing the contribution of individual genes is likely to be very complex, as some modify the impact of other genes and other environmental factors rather than incurring a direct, easily attributable effect. The two dominant predisposing syndromes are familial adenomatous polyposis and Lynch syndrome, the first due to a mutant tumour-suppressor gene APC, and the second due to mutations in a number of genes responsible for mismatch repair in DNA at cell division. Establishing genetic susceptibility for colorectal cancer will soon be possible, and could save lives by allowing targetting of screening and the encouragement of preventive behaviours. However, there will always be a risk of making healthy people "sick" through the identification of predisposing genes, and there are many potential ways by which a gene carrier may be stigmatized by society, insurance companies and employers.

Aged↗
PubMed1999

Genetic predictive testing for bowel cancer predisposition: the impact on the individual.

When considering the impact of a genetic diagnosis of hereditary predisposition to colon cancer, there are many similarities to other predictive genetic tests, but also many differences. The development and availability of such genetic diagnoses, and the concept of testing being linked to effective prevention, have advanced rapidly, opening up not only unique opportunities but also unique psychosocial situations for the affected families-and unusual ethical issues for the professional. Compared to a diagnosis of sporadic colorectal cancer for a patient, hereditary colorectal cancer requires an understanding of genetics, heredity, and the attendant mathematics of risk calculation, but, most importantly, there must be a belief that it is possible to remain healthy whilst having an increased risk. This paper outlines the possible impact of a genetic diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP) on both the individual and the family and concludes that genetic testing should be accompanied by genetic counseling. Relevant ethical issues are also introduced, with the opinion presented suggesting that if primary considerations are always for the individual rather than the family or society, then unethical or eugenic decisions are likely to be avoided.

Adenomatous Polyposis Coli↗
PubMed1997

Endoscopic screening and surgery for familial adenomatous polyposis: dangerous delays.

BACKGROUND: Registries for patients with familial adenomatous polyposis (FAP) can improve patient management. However, in relation to colorectal cancer, a critical review has not previously been undertaken of the effectiveness of screening and surgical protocols within a registry. METHODS: A review was undertaken of 63 gene carriers who received primary treatment for FAP between 1987, when the Northern Region Polyposis Registry was formed, and 1995. RESULTS: In some gene carriers with colorectal cancer, surgery was delayed because of social factors or unpleasant surgical experiences in the family. Colonoscopy failed to detect five colorectal cancers. CONCLUSIONS: Delays in treatment still occur in patients with FAP and colorectal cancer, often because of complex social problems and patients' fear of surgery. If multiple colorectal polyps are present, colonoscopy is not a reliable screening test for malignancy and prophylactic surgery is indicated, preferably before the patient is 20 years old.

Adenomatous Polyposis Coli↗
PubMed1996

Direct comparison of monophasic, biphasic and sequential pulse defibrillation over a single current pathway.

BACKGROUND: Defibrillation waveform and its spatial and temporal distribution are important determinants of its efficacy. Previous comparisons of monophasic, biphasic and sequential waveforms have used one current pathway for monophasic and biphasic defibrillation and two pathways for sequential defibrillation thus confounding a direct comparison of the waveforms. DESIGN: This study compared monophasic, biphasic and sequential pulse defibrillation over a single current pathway using a nonthoracotomy and a thoracotomy lead system in a dog model. MAIN RESULTS: Eight mongrel dogs (mean weight 21.6+/-2.9 kg) first underwent nonthoracotomy defibrillation testing followed by a median sternotomy and implantation of two 13.9 cm2 epicardial patch electrodes posterior = cathode). Nonthoracotomy electrode configuration consisted of a right ventricular catheter (cathode) and a chest wall subcutaneous patch (anode). After 10 s of alternating current induced ventricular fibrillation, defibrillation was attempted with a test shock. Monophasic, biphasic and sequential shocks of 10 ms total duration were compared. Biphasic and sequential shocks consisted of two 5 ms components separated by 0.25 ms switch time constant. Four trials of five leading edge voltages were performed for each waveform and stepwise logistic regression analysis was used to determine 80% probability of successful defibrillation (E80). For epicardial defibrillation, E80s were monophasic 11.3+/-1.5 J; biphasic 7.9+/-1.2 J; and sequential 12.1+/-1.4 J. For nonthoracotomy defibrillation, E80s were monophasic 17.7+/-3.4 J; biphasic 13.8+/-3.3 J; and sequential 18.2+/-3.5 J. The mean E80 for biphasic pulses was significantly lower than monophasic or sequential pulses for either lead system. CONCLUSIONS: Biphasic pulses are superior to monophasic or sequential pulses delivered over a single current pathway.

Animals↗
PubMed1995

Comparison of monophasic and biphasic defibrillating pulse waveforms for transthoracic cardioversion. Biphasic Waveform Defibrillation Investigators.

All transthoracic defibrillators on the US market use nominally monophasic shock waveforms. However, biphasic waveforms have a lower defibrillation threshold than monophasic waveforms for transthoracic defibrillation of animals and for defibrillation of humans by implantable cardioverter defibrillators. The relative efficacies of Edmark monophasic and Gurvich biphasic transthoracic cardioversion waveforms (200 J into 50 omega) were compared for transthoracic cardioversion in 171 patients undergoing electrophysiologic study for evaluation of ventricular arrhythmias. Patients were randomized in a blinded fashion to receive either a monophasic or a biphasic waveform for the initial shock for conversion of induced ventricular arrhythmias (ventricular fibrillation [VF] = 53, monomorphic ventricular tachycardia [VT] = 80, polymorphic VT = 30, ventricular flutter = 8). Delivered energies for the Edmark and Gurvich waveforms were 215 +/- 11 and 171 +/- 11 J, respectively. There were no significant differences in patient characteristics, use of antiarrhythmic agents, arrhythmia cycle length, or duration of arrhythmia prior to shock for monophasic and biphasic waveform groups. The first shock for all arrhythmias was successful in 75 of 88 patients (85.2%) for the monophasic waveform compared with 81 of 83 patients (97.6%) for the biphasic waveform, p = 0.0054. The first shock for VF was successful in 22 of 28 patients (78.6%) for the monophasic waveform compared with 25 of 25 (100%) for the biphasic waveform, p = 0.0241. The Gurvich biphasic waveforms delivering a mean of 171 J were superior to Edmark monophasic waveforms delivering a mean of 215 J for transthoracic cardioversion of arrhythmias of short duration. This finding may have important implications for the development of future transthoracic defibrillators.

Adult↗
PubMed1995

Clinical impact of colonoscopic screening in first-degree relatives of patients with hereditary non-polyposis colorectal cancer.

Sixty-one asymptomatic individuals with an affected first-degree relative from five large hereditary non-polyposis colorectal cancer (HNPCC) kindreds were screened by colonoscopy. Neoplasms were found in nine (15 per cent) of 61 individuals on the first screen. Five subjects had a single adenoma while two had two adenomas each. There were two patients (3 per cent) with malignant neoplasms: one with a Dukes B adenocarcinoma and one with synchronous Dukes C adenocarcinomas in the caecum and ascending colon. These findings support the hypothesis that adenomas do not occur in large numbers in HNPCC families but, because of the high malignant conversion rate, biennial colonoscopy with removal of polyps seen is recommended.

Adenocarcinoma↗
PubMed1995

A direct comparison of epicardial and nonthoracotomy defibrillation using monophasic and biphasic shocks.

Defibrillation using epicardial patches may be associated with lower energy requirements than nonthoracotomy defibrillation although a direct comparison using various waveforms has not been reported. To directly compare defibrillation efficacy using these two configurations, nine mongrel dogs (20.9 +/- 2.3 kg) first underwent nonthoracotomy defibrillation testing followed by a thoracotomy and implantation of epicardial patch electrodes and redetermination of defibrillation efficacy. Each dog served as its own control. Nonthoracotomy electrode configuration consisted of a right ventricular catheter (cathode) and a chest wall subcutaneous patch (anode). The epicardial configuration consisted of two 13.9 cm2 epicardial patches. Alternating current induced ventricular fibrillation was allowed to persist for 10 seconds, followed by either a monophasic or a single capacitor biphasic shock of 10-msec total duration. Four trials of five leading edge voltages were performed for monophasic and biphasic pulses and stepwise logistic regression analysis was used to determine 80% probability of successful defibrillation (E80). For epicardial defibrillation E80s were: monophasic 19.2 +/- 4.2 J and biphasic 12.6 +/- 4.0 J; nonthoracotomy defibrillation E80s were: monophasic 24.2 +/- 4.4 J and biphasic 17.8 +/- 4.1 J. Epicardial patch defibrillation required less energy than nonthoracotomy electrode configuration. However, using biphasic pulses nonthoracotomy defibrillation could achieve lower defibrillation energy requirements than epicardial defibrillation with monophasic pulses.

Animals↗
PubMed1994

Electrode polarity is an important determinant of defibrillation efficacy using a nonthoracotomy system.

Experimental and clinical data using epicardial patch electrodes and monophasic waveform suggest that electrode polarity may be an important determinant of defibrillation efficacy. Our objective was to examine the effect of electrode polarity in an animal model using a nonthoracotomy system and monophasic and biphasic waveforms for defibrillation. We examined the effect of lead polarity in 14 pentobarbital anesthetized dogs (21.1 +/- 2.4 kg) using monophasic and biphasic shocks and a nonthoracotomy system. Monophasic and single capacitor biphasic shocks of 10-msec total duration were used. The lead system consisted of a right ventricular catheter electrode with 4-cm2 surface area and a left chest wall subcutaneous patch electrode with 13.9-cm2 surface area. Electrode polarities RV(-)-Patch(+) and RV(+)Patch(-) were tested using both monophasic and biphasic waveforms. Alternating current was used to induce ventricular fibrillation and test shocks were delivered after 10 seconds of ventricular fibrillation. Each polarity configuration for monophasic and biphasic waveforms was tested four times at five different capacitor voltage levels (200-600 V, in 100-V increments). Defibrillation efficacy curves were constructed using logistic regression analysis for each animal and energies associated with 80% probability of successful defibrillation (E80) were determined. The mean E80 +/- SD values were as follows. Monophasic waveform: RV(-)Patch(+) 23.4 +/- 7.5 J; RV(+)Patch(-) 20.9 +/- 7.9 J (P < 0.03). Biphasic waveform: RV(-)Patch(+) 15.8 +/- 6.8 J; RV(+)Patch(-) 12.5 +/- 6.0 J (P < 0.03). The mean impedance values for both waveforms using either polarity ranged from 65.4 to 67 ohms and were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pericardial effusion increases defibrillation energy requirement.

Pericardial effusion may increase defibrillation energy requirements. We examined the effect of pericardial effusion in seven pentobarbital anesthetized dogs (25.3 +/- 3.4 kg) using monophasic and biphasic shock. A median sternotomy was performed and two 13.9 cm2 patch electrodes were sewn extrapericardially; 3 cc/kg of 0.9% NaCl was instilled through an intrapericardial catheter used to create a hemodynamically insignificant pericardial effusion. Four trials of five leading edge voltages (200-600 volts, in 100 volt increments) were performed for monophasic and biphasic shocks of 10 msec total duration and defibrillation efficacy curves were determined by logistic regression analysis. Baseline impedance was 68.1 and 66.2 Ohms for monophasic and biphasic waveforms, respectively, and decreased to 52.9 and 49.9 Ohms, respectively, with pericardial effusion (P < 0.01). Energy associated with 80% probability of successful defibrillation (E80) for monophasic shock was 16.0 joules at baseline and increased to 18.5 joules with pericardial effusion (P < 0.016). Similarly, E80 for biphasic shocks increased from 10.6 joules to 13.0 joules (P < 0.016). Removal of pericardial effusion was associated with impedance and E80 returning to baseline. In this model, pericardial effusion increased defibrillation energy requirements and may explain early postimplant defibrillator failure.

Animals↗
PubMed1993

Colonic fermentation of complex carbohydrates in patients with familial adenomatous polyposis.

Decreased production of butyric acid by colonic carbohydrate fermentation may predispose to colonic carcinogenesis, with the implicit assumption that the decrease in faecal butyrate found predates the development of the tumour. The influence of the genetic predisposition to colonic tumours and the presence of colonic polyps on in vitro fermentation of carbohydrates was examined. Stool samples from 11 normal controls and 20 patients with familial adenomatous polyposis (FAP) were incubated anaerobically with a range of carbohydrates. Fermentation patterns were similar for glucose and raffinose. These sugars produced different short chain fatty acid (SCFA) patterns from the two polysaccharides, starch and arabinogalactan, which differed one from the other. The FAP gene carriers with polyps produced less butyrate than normal controls (p < 0.005) and gene carriers without polyps (p < 0.05). There were corresponding decreases in the molar ratios of butyrate. Gene carriers without polyps produced less absolute amounts of acetate than normal controls (p < 0.05) and slightly less total SCFAs (p < 0.05) but were otherwise not significantly different. The decreased production of butyrate noted by other workers may be secondary to the tumours rather than a contributory cause.

Adenomatous Polyposis Coli↗
PubMed1992

Efficacy and safety of transcutaneous low-impedance cardiac pacing in human volunteers using conventional polymeric defibrillation pads.

STUDY OBJECTIVES: To assess the safety and efficacy of transcutaneous cardiac pacing using low-impedance defibrillation-type, self-adhesive polymer electrode pads positioned in the same anatomic sites typical of such pad placement in emergency defibrillation attempts. DESIGN: Prospective, randomized, single-blinded normal subject investigation. METHODS: Thirty healthy unmedicated adult volunteers of both sexes were paced transcutaneously to the threshold of capture and beyond by an intensity factor of 125%. A commercial defibrillator-pacer operating in demand mode had its rate set-point higher than the subjects' base-line rate by 125%. Threshold was established as the pulse current required to effect 75% captured beats. Pacing was continued at the 125% level for two minutes, during which subjective discomfort levels were recorded on a 1-to-5 pain scale. RESULTS: All subjects but one were able to complete the study as designed. The single exception complained of intolerable pain early in the two-minute trial. Capture current had a mean value of 80 mA while the pain assessment averaged 3.2 on our five-point scale. No subject showed any untoward cardiovascular effects either during or after the study. CONCLUSION: In normal human volunteers, transcutaneous cardiac pacing with low-impedance polymer pad electrodes is safe. By extrapolation from this study population, it is sufficiently effective to accommodate successfully the vast majority of clinical circumstances likely to be encountered in emergency medicine.

Adult↗
PubMed1991

Role of a regional register for familial adenomatous polyposis: experience in the northern region.

Within 36 months of its formation the Northern Region Polyposis Registry had increased the number of identified gene carriers of familial adenomatous polyposis from 56 to 65 in a population of 3.1 million and had achieved a 15-fold increase in the number of at-risk relatives being regularly screened. Review of the surgical records at the outset of the registry revealed that the mean age at diagnosis of those patients detected by screening was 24.7 years, whereas it was 36.6 years for those detected by symptoms. Ten of the 31 in the latter group had colorectal carcinomas whilst only one of those detected by screening had a cancer and a significantly higher proportion had sphincter-saving surgery. A regional registry can provide an effective screening and counselling service to surgeons treating patients with familial adenomatous polyposis. At-risk relatives are best assessed by combining results of the different screening procedures now available but the prime requirement of a successful registry is dedicated domiciliary counselling.

Adenomatous Polyposis Coli↗
PubMed1991

Comparison of morbidity and function after colectomy with ileorectal anastomosis or restorative proctocolectomy for familial adenomatous polyposis.

Restorative proctocolectomy with an ileal reservoir (RPC) should prevent colorectal cancer in patients with familial adenomatous polyposis. Until this is confirmed its role compared with total colectomy and ileorectal anastomosis (IRA) will depend on the relative morbidity and postoperative bowel function after the two procedures. This was analysed in 99 patients (37 RPC, 62 IRA) operated on between 1977 and 1989. Morbidity was greater after RPC with subsequent ileostomy closure (median hospital stay, 24 versus 11 days; complications, 60 versus 21 per cent; reoperation, 29 versus 3 per cent; return to normal activity; 31 versus 14 weeks). There was little difference in bowel function; after IRA median frequency was 3/24 h and urgency (unable to wait 15 min) occurred in 50 per cent, compared with 4.5/24h and 17 per cent after RPC. Night evacuation occurred in 10 and 43 per cent respectively. IRA was performed in younger patients (median 19 versus 31 years) who had fewer bowel motions before operation (2 versus 5/24 h). The greater morbidity of RPC suggests that it should be restricted to patients at higher risk of developing later rectal cancer, including those unavailable for follow-up and those with large or confluent rectal polyps or with curable colon cancer at the initial colectomy.

Adenomatous Polyposis Coli↗