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Biomedical subjects

C M White

Publications and source records attributed to C M White.

At least 109 records · Page 6Linked to original sources
PubMed1986

Accumulation and persistence of DNA adducts in respiratory tissue of rats following multiple administrations of the tobacco specific carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone.

4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a major nitrosamine formed in tobacco smoke, induces a high incidence of lung, liver, and nasal cavity tumors in rats. Since alpha-hydroxylation of NNK by target tissues can lead to the generation of a methylating agent, the formation and removal of 7-methylguanine and the promutagenic lesions O6-methylguanine (O6mGua) and O4-methyldeoxythymidine were determined over 12 days of NNK administration to rats (100 mg/kg/day). DNA alkylation was greatest in the nasal mucosa, followed by liver and lung after 1 dose of NNK. No DNA adducts were detected in kidney and brain under these conditions. The concentration of O6mGua increased steadily in lung throughout the treatment regimen, while O6-methylguanine-DNA methyltransferase decreased to less than 5% of control. The concentration of O4-methyldeoxythymidine in lung DNA reached a steady state after 4 days of carcinogen treatment. After NNK treatment was discontinued, O6mGua persisted, while O4-methyldeoxythymidine was removed rapidly in the lung, suggesting that different repair pathways exist for the removal of these adducts in vivo. In hepatocytes, nonparenchymal cells, and nasal mucosa, O6mGua concentrations were maximal after 1-2 days and declined by 50-80% during the remaining 10 days of treatment. The decrease in O6mGua levels in nasal mucosa paralleled a decline in O6-methylguanine-DNA methyltransferase activity and was associated with marked cytotoxicity to Bowman's glands, portions of the lateral nasal gland, and the olfactory and respiratory mucosa during carcinogen treatment. In contrast, the decline in O6mGua in hepatocytes was attributed to the induction of O6-methylguanine-DNA methyltransferase activity, since an 18-fold reduction in the ratio of O6mGua:7-methylguanine was observed over the 12 days of treatment. These studies have demonstrated a marked accumulation of promutagenic DNA adducts in target tissues during repeated exposure to NNK.

Animals↗
PubMed1985

Immediate colectomy and primary anastomosis for acute obstruction due to carcinoma of the left colon and rectum.

A consecutive series of 35 patients with acute obstruction due to carcinoma of the left colon (29) or rectum (six) were treated by primary resection with anastomosis. The operation usually took the form of a left hemicolectomy or sigmoid resection without a proximal colostomy. There were three operative deaths (8.5 percent) due to anastomotic dehiscence, bronchopneumonia, and pulmonary embolism, respectively. Nonlethal complications occurred in ten patients (anastomotic leakage in three, a ureteric fistula in one, and wound infection in six). The mean duration of hospital stay in patients without complications was 18 days (range, 12 to 35). The morbidity and mortality in this series did not exceed the cumulative morbidity and mortality that would be expected after staged surgery. Compared with staged surgery, immediate resection and anastomosis, by avoiding the problems of colostomy and reducing the length of hospital stay, have significant advantages for the patient.

Aged↗
PubMed1984

The importance of the distal stomach in gastric emptying of liquids in man.

The effects of pyloroplasty and vagal denervation of the distal stomach on gastric emptying of 10% dextrose have been compared. In a randomized trial, 38 male patients having elective surgery were treated by proximal gastric vagotomy (PGV, N = 10), proximal gastric vagotomy and pyloroplasty (PGV + P, N = 9), total gastric vagotomy (TGV, N = 9), and total gastric vagotomy and pyloroplasty (TGV + P, N = 10). Gastric emptying was recorded using an external scanning technique before and after operation. Compared with before operation, all four procedures resulted in significantly faster emptying during ingestion of the meal (the filling phase). This is attributable to failure of receptive relaxation of the proximal stomach. The emptying phase (after ingestion of the meal) was unchanged by PGV, but was significantly altered by PGV + P, TGV, and TGV + P (Principal Component Analysis). Before operation and after PGV, emptying fitted a monoexponential curve. In contrast, after PGV + P, TGV, and TGV + P, the emptying phase fitted a double exponential curve. Emptying was precipitate initially, but slowed later, leaving a large residual volume. We conclude that, when the proximal stomach is denervated, the intact, innervated distal stomach can restore the emptying of hypertonic dextrose to normal; however, when the distal stomach is denervated or pyloroplasty has been performed emptying remains uncontrolled. Since pyloroplasty and vagal denervation have the same effect, it is concluded that the mechanism retarding the emptying of hypertonic dextrose is an active mechanism that resides in the terminal antrum or pylorus.

Adult↗
PubMed1983

Effects of nutrient liquids on human gastroduodenal motor activity.

The effects of intragastric infusion of 10% Intralipid and 10% dextrose on the intraluminal pressures in the antrum, pylorus and duodenal bulb have been examined. Ten studies with each infusate have been performed in 10 normal subjects and the results compared with those obtained previously in 22 studies during intragastric infusion of isotonic saline. During saline infusion, contractile activity varied. In six studies fasting motor activity persisted; in the remainder, variable activity, without recognisable pattern was recorded. With saline, the gastroduodenal region usually functioned as a unit and the pylorus was the least autonomous part. Neither a sustained rise of basal pressure nor rhythmic, independent contractions were recorded from the pylorus. The contractile activity of the gastroduodenal region with Intralipid and dextrose was more uniform than with saline. Fasting motor activity was always abolished. The gastroduodenal region ceased to contract as a unit and the pylorus acquired autonomous activity. Rhythmic, independent contractions of the pylorus were recorded in nine of 10 studies during Intralipid infusion and six of 10 studies with dextrose. In addition, a sustained rise in pyloric basal pressure was recorded in eight of 10 studies with Intralipid and three of 10 studies with dextrose. Pyloric motility indices were significantly greater with fat than with dextrose. The observed differences in gastroduodenal motility are consistent with a role for the pylorus in the control of emptying of liquid from the stomach.

Duodenum↗
PubMed1983

Dose-response relationships for the binding of benzo(a)pyrene metabolites to DNA and protein in lung, liver, and forestomach of control and butylated hydroxyanisole-treated mice.

In this study, the formation of benzo(a)pyrene (BP) metabolite:DNA adducts in lung, liver, and forestomach of control and butylated hydroxyanisole (BHA)-treated (5 mg/g diet) female A/HeJ mice was examined as a function of BP dose (p.o.), ranging from 2 to 1351 mumol/kg. The major identified adduct in each tissue at each dose was the (+)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEI):deoxyguanosine adduct. A 7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene:deoxyguanosine adduct, a(-)-BPDEI:deoxyguanosine adduct, and an unidentified adduct were also observed. In lung and liver of untreated animals, the dose-response curves for BPDEI:DNA adduct levels were sigmoidal. In forestomach, there was no indication of saturation of DNA binding over the BP dose range examined. The dose-response curves became linear as BP dose approached zero and thus, no threshold dose existed below which binding of BPDEI to DNA did not occur, at least in lung, liver, and forestomach of these mice. In forestomach, the dose-response curve for BPDEI:DNA adducts in BHA-treated mice, 0.5% of diet for 2 weeks, was parallel to the curve for control animals and thus, the inhibition (45%) of adduct formation is independent of BP dose. In contrast, BHA treatment diminished the curvilinear nature of the dose-response curves for BPDE adducts in lung and liver. The inhibition of BPDEI:DNA adduct formation by BHA in lung and liver was dose dependent. The inhibition of lung (68%) and liver (82%) adduct formation was highest at a BP dose of 270 mumol/kg. As the BP dose approached zero, the inhibition of BPDEI:DNA adduct formation by BHA decreased with BP dose and approached values of approximately 40% (lung) and 55% (liver). The dose dependency of the binding of BP metabolites to protein was also examined. BPDEI:DNA adduct concentrations ranged from 2 to 10% of protein binding concentrations in liver of untreated animals, from 3 to 7% in forestomach, and from 5 to 7% in lung. The dose-response curves for protein binding of BP metabolites in lung and liver from BHA-treated animals were essentially parallel to those in control animals and thus, the inhibition of protein binding by BHA treatment had no dose dependency in these organs. No consistent BHA effect was observed on the amount of binding of BP metabolites to forestomach protein.

Animals↗
PubMed1982

Application of gravitational clustering analysis to liquid gastric emptying.

A gravitational clustering analysis was applied to principal component weighting factors and t1/2 values from 100 liquid gastric emptying studies. Using principal components, groups of patients with clinical features in common were identified, whereas the analysis of the t1/2 values failed to differentiate them.

Duodenal Ulcer↗
PubMed1981

A study of motility of normal human gastroduodenal region.

A method of recording continuously and simultaneously the intraluminal pressure in the antrum, pylorus, and duodenal bulb has been used to study gastroduodenal motility during intragastric infusion of saline. Twenty-two studies were performed in 15 normal individuals. Two types of contraction were recorded: (1) independent contractions of the individual parts of the gastroduodenal region, and (2) related contractions of the antrum, pylorus, and duodenal bulb, resulting in a concerted contraction of the whole region. The majority of pyloric contractions were part of a concerted contraction of the whole gastroduodenal region during which the pylorus behaved as the terminal part of the antrum. The majority of duodenal contractions were not associated with pyloric contractions, only 21.7% of duodenal contractions coincided with closure of the pylorus. This suggests that under the conditions of this study the pylorus was not acting as a barrier to reflux. An elevated basal pressure was never recorded from within the pylorus; apart from a brief closure during contraction, the pylorus is always open.

Adult↗
PubMed1980

The occult rectal prolapse syndrome.

Occult rectal prolapse is a condition of young adults which causes problems in diagnosis. Symptoms consist of tenesmus and the passage of blood and mucus associated with constipation and straining at stool. The rectal prolapse often remains unrecognized for a long time because demonstration of the prolapse is difficult. There are characteristic changes in the rectum on clinical examination and these should alert the clinician to the diagnosis. Treatment of the prolapse relieves the symptoms.

Adolescent↗
PubMed1979

The effect of oxygen concentration on the X-ray induction of chromosome aberrations in human lymphocytes.

In vitro dose--response curves, for unstable chromosome aberration induction in human lymphocytes under conditions of full oxygenation or of anoxia, have been obtained using 250 kVp X-rays. Dicentric yields have been fitted to the quadratic function Y = alpha D + beta D2. An Oxygen Enhancement Ratio (OER) ranging from 7.2 to 2.7 was calculated from the coefficients of these curves possibly indicating that the data do not fit to the dose-modifying model of the oxygen effect although the differences are not statistically significant. A similar analysis of total aberration data yields an OER of 3.6 to 2.7 fitting much more satisfactorily to the dose-modifying model. Variations in dicentric yield induced by 3.0 Gy and 0.75 Gy of X-rays with increasing oxygen concentration were plotted and for each dose a constant dicentric yield was observed at oxygen levels of 2 and 250 ppm. Above 250 ppm yields increased steeply up to about 1% oxygen and then more gradually to a maximum at 100% oxygen.

Chromosome Aberrations↗
PubMed1978

Gastric emptying after treatment of stenosis secondary to duodenal ulceration by proximal gastric vagotomy and duodenoplasty or pyloric dilatation.

A consecutive series of 12 patients with stenosis secondary to duodenal ulceration were treated by proximal gastric vagotomy (PGV) and duodenoplasty or PGV and dilatation of the stenosis. Three months after operation the rate and pattern of gastric emptying of a solid meal was measured in each patient and compared with 18 patients with uncomplicated duodenal ulcer treated by PGV alone. Two patients developed gastric stasis in the early postoperative period which resolved with medical treatment. All patients were asymptomatic and were eating normally three months after operation. There was no significant difference in the rate of gastric emptying postoperatively between the patients who had stenosis and those who had uncomplicated duodenal ulcers. These results indicate that despite early postoperative difficulties in some patients pyloric dilatation or duodenoplasty with PGV are both effective treatments for stenosis due to duodenal ulceration.

Adult↗