Biomedical subjects
Publications and source records attributed to I C Roberts-Thomson.
Three patients with histiocytic lymphoma presented with jaundice due to extrahepatic biliary obstruction. Two had widespread disease, but one had a primary lymphoma of the head of the pancreas simulating pancreatic cancer. Biliary bypass surgery was avoided in two patients, both of whom showed resolution of jaundice following treatment with cytotoxic chemotherapeutic drugs.
Endoscopic sphincterotomy was performed in 53 patients with biliary tract disease who were considered to be at high risk from conventional surgical procedures. Forty-five patients had choledocholithiasis, while eight had miscellaneous disorders including carcinoma, stenosis of the papilla, and postoperative biliary fistulae. Forty-three of 45 patients with choledocholithiasis have been free of symptoms since the procedure, and most have had repeat retrograde cholangiography confirming the absence of bile duct-stones. Endoscopic sphincterotomy is a safe and effective procedure in selected high-risk patients, particularly those with choledocholithiasis after cholecystectomy.
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When C3H/He mice are dosed orally with fecal cysts or trophozoites of the intestinal parasite, Giardia muris, they become chronically infected, whereas BALB/c (or DBA/2) mice rapidly eliminate their infection. The ability to eliminate a primary infection or resist a challenge infection was not related to levels of serum IgA antibody directed against a crude extract of trophozoites. The possibility that the development of host-protective immunity may either be delayed or absent in C3H/He mice was investigated by 2 types of experiment: 1) BALB/c and C3H/He mice were drug-cured at various times after a primary infection and assessed for their ability to resist reinfection, and 2) the ability of infected female mice to protect their suckling young was assessed. Under these experimental conditions, no significant difference in the kinetics of development of resistance to a challenge infection was noted. Thus, mice of both strains were capable of resisting a challenge infection after drug-cured and infected mothers were able to protect their suckling young from a challenge infection. Drug-cured long-term infected mice were resistant to a challenge of either cysts or trophozoites obtained from either 1-wk infected nude mice or long-term infected C2H/He mice. Thus, it is unlikely that the explanation for chronic infection oif C3H/He mice is that variants or a modified population of G. muris trophozoites arise to which C3H/He mice have a defective response. The possibility that G. muris is able to suppress host-protective responses in chronically-infected C3H/He mice but not in BALB/c mice is discussed.
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Juxtapapillary duodenal diverticula were identified at duodenal endoscopy in 42 (9%) of 470 consecutive patients undergoing endoscopic retrograde cholangiopancreatography. Patients with duodenal diverticula had a higher frequency of gallstones disease (52% versus 35%) and of relapsing or chronic pancreatitis (26% versus 14%) and a higher frequency of recurrent bile duct calculi after biliary surgery (12% versus 2%). The association between gallstone disease and duodenal diverticula was corroborated by a second study showing a significantly higher frequency of gallstones in 350 patients who had a duodenal diverticulum on barium-meal X-ray examination.
Genetic markers were analysed in 48 adults who appeared to have a prolonged infection with Giardia lamblia. The frequency of ABO blood groups, Rhesus blood groups, and Gm phenotypes was similar to that in control subjects. However, there was a higher than expected frequency of HLA antigens A1 (observed 46 . 7%, expected 32%) and B12 (observed 47 . 8%, expected 25 . 8%) and a higher than expected frequency of the phenotypes A1/A2 and B12/B27. Genetic studies were also performed with inbred strains of mice showing relatively rapid (BALB/c) and defective (C3H/He) spontaneous elimination of Giardia muris. From analysis in backcross mice several genes appeared to influence susceptibility to prolonged infection with G. muris.
Duct aspiration was performed immediately after endoscopic retrograde cholangiopancreatography (ERCP) in 33 patients with ductal changes which were suggestive of pancreatic or biliary cancer. Malignant cells were identified in 10 of 17 patients (60%) with cancer of the pancreas, and in two of 10 patients (20%) with cancer of the biliary tract. Atypical cells were identified in additional patients with cancer, but cytological characteristics did not permit a definitive diagnosis. No false positive diagnoses were made. Duct aspiration is a relatively simple extension of ERCP, and enhances diagnostic accuracy, particularly in patients with carcinoma of the pancreas.
Intrapancreatic cysts were demonstrated by endoscopic retrograde pancreatography (E.R.P.) in nine patients with a clinical diagnosis of relapsing pancreatitis. The cysts ranged in diameter from 0.6 cm to 5 cm and were frequently associated with a prolonged elevation of the serum amylase level. The complication of intracystic haemorrhage with obstructive jaundice developed in one patient requiring early surgical decompression and drainage. In four patients laparotomy was performed because of continuing abdominal pain. One patient was treated by cystogastrostomy and another by cyst aspiration, but in two patients the cyst could not be visualized or palpated. Four patients were observed without operation for periods of four to 24 months, and all showed improvement or resolution of symptoms. E.R.P. was repeated in one patient and the cyst could not be outlined, while in another an abnormal barium meal X-ray examination result reverted to normal. Intrapancreatic cysts can be managed non-operatively, since complications appear infrequent and spontaneous resolution may occur.
Strains of mice showing relatively rapid (BALB/c) and defective (C3H/He) spontaneous elimination of Giardia muris displayed marked differences in the degree of resistance to infection induced by prior injection of trophozoites in Freund complete adjuvant.
Endoscopic retrograde cholangiopancreatography involves endoscopic visualization of the papilla of Vater, placement of a cannula in the orifice of the papilla and contrast radiology of pancreatic and biliary ducts. With experience, the procedure can be performed relatively rapidly with visualization of the desired duct in the majority of patients, and a low frequency of complications. The technique appears to be highly sensitive and specific for the diagnosis of biliary and pancreatic disease. Valuable additional information may be obtained from duodenal endoscopy, duodenal biopsy and duct aspiration for cytological studies. An extension of the technique--endoscopic sphincterotomy of the papilla of Vater--has become a therapeutic option in selected patients with choledocholithiasis.
Endoscopic retrograde cholangiopancreatography (ERCP) involves cannulation of the papilla of Vater followed by contrast radiology of the biliary and pancreatic ducts. With experience, X-ray films of the desired duct(s) can be obtained in 90% of patients, with minimal patient discomfort and a low frequency of complications. Retrograde cholangiography accurately assesses the site and cause of biliary tract obstruction. Retrograde pancreatography reveals ductal abnormalities in most patients with chronic pancreatitis and pancreatic cancer, and the nature of the abnormality usually permits differentiation of the two diseases. The diagnostic accuracy of ERCP is enhanced by cytological evaluation of pure pancreatic juice, while endoscopic sphincterotomy is a therapeutic option in selected patients with choledocholithiasis and papillary stenosis. Current developments include endoscopic aspiration biopsy of the pancreas and endoscopy of pancreatic and biliary ducts, using a miniature endoscope passed down a channel in the parent instrument.
The natural history of Giardia muris has been studied in inbred mouse strains and hypothymic (nude) mice derived from a specific pathogen-free facility. Although giardiasis was readily established in several mouse strains, marked variation was observed in the time course of spontaneous elimination of the parasite. During a 10-week study, fecal excretion of Giardia cysts remained relatively constant in C3H/He mice, but decreased at a variable rate in other mouse strains. Resistance to reinfection was greater in strains in which the duration of primary infection was relatively short. Hypothymic (nude) mice derived from a strain showing a relatively rapid elimination of Giardia (BALB/c) maintained a stable infection with high cyst counts. Nude mice reconstituted with lymphoid cells from syngeneic thymus-intact mice showed a progressive reduction in cyst excretion and reconstitution with limited numbers of lymphoid cells from thymus-intact mice previously exposed to Giardia accelerated resolution of infection. In nude mice, giardiasis was associated with a reduction in the villus-crypt ratio of jejunal mucosa, but the degree of change was greater in nude mice reconstituted with lymphoid cells. This Giardia model involving inbred strains and nude mice permits further dissection of the function of thymus-derived cells in intestinal immune responses and induction of changes in small bowel morphology.
The interaction of the intestinal phases of Giardia muris and Trichinella spiralis was investigated in Swiss albino mice. Intraoesophageal inoculation of G. muris cysts seven days before, or seven days after, similar inoculation of T. spiralis larvae resulted in significant reduction in the numbers of Giardia trophozoites in small bowel and Giardia cysts in stools. This effect was not observed when G. muris cysts were administered after resolution of the intestinal phase of trichinosis. Giardiasis had no effect on trichinosis as assessed by numbers of adult worms in small bowel and larvae in skeletal muscles. Studies of small bowel morphology showed that the intestinal phase of trichinosis was associated with increased numbers of inflammatory cells in the lamina propria, a significant increase in Paneth cells in crypts, and a marked reduction in the villus:crypt ratio of jejunum. These observations suggest that the intestinal phase of trichinosis induced environmental changes in small bowel, perhaps related to inflammation, which resulted in suppression of proliferation of Giardia trophozoites.
An animal model for giardiasis was developed using Giardia muris in Swiss albino mice. Intraesophageal inoculation of G. muris cysts caused a reproducible pattern of infection, with trophozoite and cyst counts reaching a maximum on days 5 to 14 after cyst inoculation and thereafter showing a progressive decline. Spontaneous resolution of infection occurred in most mice after 21 to 28 days. When compared to uninfected controls, Giardia-infected mice had significant impairment of weight gain and a significant reduction in the villus to crypt ratio of jejunal mucosa. Although maximal trophozoite and cyst counts were independent of the size of the cyst inoculum, those mice receiving inoculations of larger numbers of cysts showed earlier attainment of maximal counts, greater impariment of weight gain, and earlier and more severe small bowel changes than mice receiving inoculations of smaller numbers of cysts. This model offers unique opportunities for study of this poorly understood gastrointestinal parasite.
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The output and concentration of gastric glycoproteins in gastric juice from patients with chronic duodenal and gastric ulcer and from controls, have been determined in the basal state and following pentagastrin stimulation. Patients with gastric ulcer had a significantly higher basal glycoprotein output, basal glycoprotein concentration and stimulated glycoprotein concentration than patients with duodenal ulcer or controls. The basal and stimulated glycoprotein output in gastric juice from patients with duodenal ulcer and controls was independent of ABO blood group and secretor status. The carbohydrate composition of the gastric glycoproteins has also been determined in the basal state, and following stimulation of gastric juice by pentagastrin, which did not influence the carbohydrate composition of the molecules. The principal carbohydrate components were galactose, N-acetylglucosamine, fucose, N-acetylgalactosamine, and sialic acid. Small amounts of mannose and glucose were detected in some gastric glycoprotein samples. The carbohydrate composition of the glycoproteins varied according to the ABO blood group and secretor status of the individual. Glycoproteins form stimulated gastric juice from non-secretors of groups A and O had a higher sialic acid content than glycoproteins from secretors of the same blood groups. There were no significant differences in the carbohydrate composition of glycoproteins from patients with chronic gastric and duodenal ulcer compared with gastric glycoproteins from control subjects of the same blood group and secretor status.