Biomedical subjects
Publications and source records attributed to J Morin.
The effect of human cytomegalovirus infection on cellular DNA synthesis in human fibroblasts was measured by fluorometry and by incorporation of radiolabeled thymidine. The results show that although HCMV infection stimulates cellular DNA synthesis in both quiescent and serum-stimulated cells, radiolabeled thymidine is almost exclusively incorporated into viral DNA.
This study was aimed to determine the effects of rilmenidine, an hypertensive drug, in an animal model of hypertension associated with insulin resistance, i.e. rats fed on a high fructose diet. Wistar rats were fed during four weeks either on a standard diet (S) or on a high fructose diet (F, 34.5% de fructose). In half of the F groups, rilmenidine (1 mg/kg/day) was added to the drinking water during the two last weeks of the diet (FR). Arterial blood pressure as well as insulin efficiency were determined at the end of the four weeks. Body weight gain was higher in F than in S rats (66 +/- 8 g versus 45 +/- 8 g; p < 0.05), this was prevented by rilmenidine treatment (32 +/- 2 g). Arterial systolic blood pressure was increased in F rats (162 +/- 2 vs 155 +/- 2 mmHg; p < 0.05), rilmenidine brought this value back to normal (149 +/- 3 mmHg). During the euglycemic hyperinsulinemic clamp, glucose utilization was lower (10 +/- 1 vs 14 +/- 1.5 mg/min/kg; p < 0.05) and hepatic glucose production higher (1 +/- 0.01 vs 0 mg/min/kg; p < 0.01) in F than in S rats. These changes in insulin action were totally abolished by rilmenidine. These data demonstrate that rilmenidine can ameliorate the deleterious effects of a high fructose diet, i.e. weight gain, hypertension and resistance to the effects of insulin Rilmenidine could represent a potential therapeutic agent for the treatment of hypertension associated with metabolic disorders such as syndrom X and obesity.
We have shown previously that fatty acid synthase (FAS) gene expression is positively regulated by glucose in rat adipose tissue and liver. In the present study, we have identified in the first intron of the gene a sequence closely related to known glucose-responsive elements such as in the L-pyruvate kinase and S14 genes, including a putative upstream stimulatory factor/major late transcription factor (USF/MLTF) binding site (E-box) (+ 292 nt to + 297 nt). Location of this sequence corresponds to a site of hypersensitivity to DNase I which is present in the liver but not in the spleen. Moreover, using this information from a preliminary report of the present work, others have shown that a + 283 nt to + 303 nt sequence of the FAS gene can confer glucose responsiveness to a heterologous promoter. The protein binding to this region has been investigated in vitro by a combination of DNase I footprinting and gel-retardation experiments with synthetic oligonucleotides and known nuclear proteins. DNase I footprinting experiments using a + 161 nt to + 405 nt fragment of the FAS gene demonstrate that a region from + 290 nt to + 316 nt is protected by nuclear extracts from liver and spleen. This region binds two ubiquitous nuclear factors, USF/MLTF and the CAAT-binding transcription factor/nuclear factor 1 (CTF/NF1). Binding of these factors is similar in nuclear extracts from liver which does or does not express the FAS gene as observed for glucose-responsive elements in the L-pyruvate kinase and S14 genes. This suggests a posttranslational modification of a factor of the complex after glucose stimulation.
OBJECTIVES: To determine the effectiveness of extracorporeal shock-wave lithotripsy (ESWL) and adjuvant bile-salt therapy for the treatment of symptomatic cholelithiasis. DESIGN: A prospective case study. Follow-up ranged from 3 to 54 months. SETTING: A university teaching hospital. PATIENTS: Two hundred and twenty-three patients with symptomatic cholelithiasis, a gallbladder that opacified at oral cholecystography and three or fewer radiolucent stones with a maximum total dimension of 3 cm. Of these patients, 197 were given bile salts (ursodeoxycholic acid or chenodeoxycholic acid, 8 to 10 mg/kg daily) and underwent ESWL. Twenty-eight were excluded because of noncompliance with the protocol or treatment failure before termination of the ESWL procedure. INTERVENTION: ESWL with a piezoelectric lithotripter. MAIN OUTCOME MEASURES: The success rate of the intervention, the causes of failure, associated complications and the recurrence rate of cholelithiasis. RESULTS: Of the 197 patients who underwent ESWL, 85 (43%) were free of stones after treatment. Treatment failure was caused by the following: unsatisfactory fragmentation (9%), increase in fragment size during bile-salt therapy (8%), severe diarrhea due to bile salts (3%), nonvisualization of fragments after the first ESWL (3%), acute cholecystitis (2%), persistence of small fragments at the end of the treatment protocol (2%) and acute pancreatitis (0.5%). Complications included biliary colic (21%), diarrhea (15%), acute cholecystitis (2.5%), acute pancreatitis (2%), macroscopic hematuria (2%), perirenal hematoma (0.5%) and vagal shock (0.5%). The recurrence rate was 18%. Causes of noncompliance with treatment (26%) were the length of treatment, the occurrence of biliary colic during this period and the high cost of bile salts. CONCLUSION: ESWL with bile salts as treatment for symptomatic cholelithiasis is not recommended for routine use.
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Expression under the control of the mouse transferrin promoter of a transgene encoding a soluble secreted derivative of the ectodomain of the human insulin receptor in transgenic mice results in the accumulation of this high-affinity insulin-binding protein in the plasma. Alterations of glucose homeostasis are observed including postabsorptive hyperglycemia concomitant with increased hepatic glucose production and hyperinsulinemia. Thus, this is the first transgenic animal model of chronic hyperglycemia with alterations in glucose homeostasis that are produced without a targeted alteration of pancreatic function. These mice provide a new experimental model to follow the progression and long-term consequences of chronic hyperglycemia.
Since laparoscopic cholecystectomy was introduced, the treatment of choledocholithiasis has been modified. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) has been performed selectively in elderly patients and in those with a strong suspicion of biliary duct stones (jaundice, demonstrated at ultrasound). Intraoperative discovery of common duct stones at cystic duct cholangiography signifies that they must be removed intraoperatively [or postoperatively by ERPC and endoscopic sphincterotomy (ES)]. As ES has a failure rate of 3-23%, laparoscopic common duct exploration emerges as the treatment of choice. Since November 1990, we have performed 59 laparoscopic common bile duct explorations. In our experience, the transcystic technique (18 patients) with choledochoscopy appears easier to perform than with fluoroscopy without choledochoscopy. Since, during our early experience, we encountered some difficulty with the transcystic technique, we elected to evaluate common duct exploration through a choledochotomy (41 patients). The main advantage of this technique is that it provides complete access to the ductal system without damage to the papilla. This procedure seems more difficult to perform than the transcystic technique and can be used when there are contraindications to the latter.
The rapid aging of the population constitutes a new challenge for the health care delivery system. This paper presents the progression of use of several diagnostic and surgical procedures in the elderly in Quebec from 1981 to 1989. Data were obtained from claims to the Régie de l'assurance maladie du Québec for the years 1981, 1985 and 1989. The rate of coronary artery bypass surgery increased by more than 700% in people 65 years and over between 1981 and 1989. This increase was especially high in the oldest age group (q 75 years). There was also a significant increase in surgery for abdominal aortic aneurysm, while the rate of carotid endarterectomy remained stable for people 65 years and over during this period. The rates of all abdominal surgical procedures examined (appendicectomy, repair of hiatal and inguinal hernia, cholecystectomy and colectomy) were relatively stable in elderly during the study period. Total hip replacement more than doubled in people 65 years and over, while other types of hip arthroplasty significantly decreased over this period. All types of diagnostic procedures examined (coronary angiography, bronchoscopy, gastroduodenoscopy and retrograd cholangio-pancreatography) increased significantly, especially in very old people. This study suggests that surgical care is increasing in the elderly in Quebec. This progression is expected to continue in the coming years so that surgical care of the elderly will become a significant part of our health care delivery system.
Between November 1990 and March 1991, five patients with cholelithiasis and associated choledocholithiasis were treated by laparoscopic cholecystectomy and common-bile-duct exploration (CBDE). Three patients had a successful CBDE, but in two common-bile-duct stones had to be extracted surgically. Two patients had formal laparoscopic CBDE, and three patients had CBDE performed through the cystic duct. All patients recovered from surgery without complication. Laparoscopic CBDE is difficult to perform because of lack of adequate instrumentation and limited experience. Although the authors do not recommend that this procedure be performed widely at present, they believe it will eventually replace many open CBDEs. The authors review the pertinent literature and evaluate diagnostic means for preoperative and peroperative detection of choledocholithiasis. They discuss the alternatives to laparoscopic CBDE, their advantages and disadvantages. Finally, they summarize their own policy with respect to laparoscopic CBDE.
Between Mar. 13 and Sept. 16, 1991, the authors performed 10 inguinal herniorrhaphies laparoscopically. Two patients with a type II hernia (indirect with dilated internal ring but intact posterior inguinal wall) had laparoscopic preperitoneal closure of the internal ring with interrupted 0-Prolene. Seven patients had a type IIIA hernia (direct), and one patient had a large type IIIB hernia (indirect with dilated internal ring and medial encroachment or destruction of transversalis fascia of Hesselbach triangle). They all underwent laparoscopic preperitoneal placement of Prolene mesh, which was fixed in place with interrupted 0-Prolene sutures. All patients recovered promptly, with less pain and minimal limping, resulting in high patient acceptance of the procedure. There were no complications. Although no recurrence was noted and the technique appears sound, it is too early to predict its long-term success. At present, the preperitoneal approach is difficult to perform because of lack of appropriate instrumentation. The surgeon who plans to perform such a procedure must be familiar with the anatomy. We suggest that every potential candidate for laparoscopic inguinal hernia repair should be apprised of the advantages and disadvantages of this approach. A research consent form should be read and signed by every patient.
Between Apr. 18, 1990, and Apr. 26, 1991, 258 patients were treated for symptomatic cholelithiasis by laparoscopic cholecystectomy. In 252 patients the diagnosis was chronic calculous cholecystitis, in 3 acute cholecystitis and in 3 hydrops of the gallbladder. There were no deaths. Major complications occurred early in the study--one patient suffered a cardiac arrest because of gas embolism and one had leakage from the stump of the cystic duct, which was treated by percutaneous drainage. Both patients recovered without further complications. The hospital stay averaged 2.9 days. The authors discuss important technical points for the safe performance of laparoscopic cholecystectomy and consider the results obtained by leading groups in the field and by one multicentre survey in the United States. Almost 25,000 cases of laparoscopic cholecystectomy are evaluated.
Between Jan. 19, 1989 and Nov. 23, 1990, 170 patients with symptomatic cholelithiasis were evaluated for possible treatment by extracorporeal shockwave lithotripsy (ESWL). Thirty-one patients were not eligible for treatment, 28 (16%) because of nonvisualization of gallstones by ultrasonography and 3 (2%) because polyps were erroneously diagnosed on ultrasonography. Thirteen (8%) patients failed to comply with the protocol, leaving 126 patients for assessment. At the time of writing, the treatment success rate is 57% at 6 months and 69% at 9 months. Treatment failed in 21 (17%) patients because of unsatisfactory fragmentation in 16 (13%) patients, frequent biliary colic in 3 (2%) patients, acute pancreatitis in 1 (0.8%) patient and severe bile-salt-induced diarrhea in 1 (0.8%) patient. Complications included biliary colic (40 patients), mild diarrhea on bile salts (24 patients), severe diarrhea (1 patient), macroscopic hematuria (4 patients), acute pancreatitis (2 patients) and vagal shock (1 patient). This study demonstrates the effectiveness (87%) of the lithotripter in reducing gallstones to fragments 5 mm in diameter or smaller. However, complete disappearance of these fragments with adjuvant bile-salt therapy may take many months.
Recombinant hepatitis B virus vaccines based on adenovirus (Ad) vectors Ad4 and Ad7 have been prepared. However, immunogenicity testing of such vaccines in experimental animals is difficult because these human adenoviruses exhibit a highly restricted host range. In this study, the dog was evaluated as a model for screening Ad4- and Ad7-vectored vaccines. Intratracheal inoculation of dogs with Ad4 and Ad7 induced substantial type-specific humoral immune responses that were significantly higher than responses obtained following pharyngeal or oral inoculations. Inoculation of dogs with recombinant Ad7 and Ad4 vaccines expressing hepatitis B surface antigen (HBsAg) elicited large antibody responses to HBsAg (anti-HBs). Substantial secondary anti-HBs responses were produced upon sequential immunizations with heterotypic Ad7 and Ad4 recombinant vaccines. These data thus indicate that the dog is a useful model for evaluating immune responses to vaccines based on Ad4 and Ad7 vectors.
A gastric [U-14C]glucose load (4.8 mg/g body wt.) was delivered to unrestrained post-absorptive or 30 h-starved rats bearing peripheral and portal vein catheters and continuously perfused with [3-3H]glucose, in order to compare their metabolic and hormonal responses. In the basal state, portal and peripheral glycaemia were less in starved rats than in rats in the post-absorptive period (P less than 0.01), whereas blood lactate was similar. Portal insulinaemia (P less than 0.05) and protal glucagonaemia (P less than 0.005) were lower in starved rats, but insulin/glucagon ratio was higher in post-absorptive rats (P less than 0.005). The glucose turnover rate was decreased by starvation (P less than 0.005). After glucose ingestion, blood glucose was similar in post-absorptive and starved rats. A large portoperipheral gradient of lactate appeared in starved rats. Portal insulinaemia reached a peak at 9 min, and was respectively 454 +/- 68 and 740 +/- 65 mu-units/ml in starved and post-absorptive rats. Portal glucagonaemia remained stable, but was higher in post-absorptive rats (P less than 0.05). At 60 min after the gastric glucose load, 30% of the glucose was delivered at the periphery in both groups. The total glucose appearance rate was higher in starved rats (P less than 0.05), as was the glucose utilization rate (P less than 0.05), whereas the rate of appearance of exogenous glucose was similar. This was due to a non-suppressed hepatic glucose production in the starved rats, whereas it was totally suppressed in post-absorptive rats. At 1 h after the glucose load, the increase in both liver and muscle glycogen concentration was greater in starved rats. Thus short-term fasting induces an increased portal lactate concentration after a glucose load, and produces a state of liver insulin unresponsiveness for glucose production, whereas the sensitivity of peripheral tissues for glucose utilization is unchanged or even increased. This might allow preferential replenishment of the peripheral stores of glycogen.
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From April to August 1990, 60 patients underwent laparoscopic cholecystectomy. Patients with biliary colic were included, but those who had florid acute cholecystitis, morbid obesity or scars in the upper portion of the abdomen were excluded. Three patients had acute cholecystitis, 56 had chronic cholecystitis and 1 had hydrops of the gallbladder. Nineteen patients had had previous lower abdominal surgery. Five patients did not require analgesia, but the remainder needed parenteral analgesia on an average of 1.7 occasions and enteral analgesia on an average of 1.8 occasions. There were no intraoperative complications, and no patient had the procedure completed by standard surgery. Postoperative hospital stay averaged 2.5 days. The mean follow-up was 39 days. Few postoperative complications were noted: two patients suffered from ileus; two patients had biliary colic postoperatively (one required endoscopic sphincterotomy with stone extraction, and in the other no common-duct stones were seen on retrograde cholangiography); one patient had an intra-abdominal abscess, which was drained percutaneously; and one patient complained of upper abdominal pain that was incisional in origin. Laparoscopic cholecystectomy should be considered the procedure of choice for elective treatment of uncomplicated symptomatic gallstone disease.
Euglycemic-hyperinsulinemic clamps coupled with an injection of [2-3H]deoxyglucose were performed in rats 1 or 6 wk after lesion of the ventromedial hypothalamus (VMH) and their age-matched controls. In the basal state, glucose utilization was not different in controls and VMH rats in all the tissues studied except in white adipose tissue where it was greatly increased after the lesion. When insulinemia was clamped at 850 microU/ml, glucose utilization was less important in glycolytic and normal in oxidative muscles in animals 1 wk after the lesion (VMH1) compared with controls. In animals 6 wk after the lesion (VMH6), all the muscles utilized less glucose than those of controls. In white adipose tissue, glucose utilization was increased twice more in VMH1 and returned to normal in VMH6. These data demonstrate a progressive development of insulin resistance in muscles. Simultaneously, there is a transient insulin hypersensitivity in white adipose tissue. This, together with a hypersecretion of insulin, could contribute to the development of body fat mass by redirecting glucose towards adipose tissue.
Extracorporeal shock-wave lithotripsy is a procedure recently introduced to treat gallstone disease. According to the literature, 15% to 25% of symptomatic persons will be candidates for this procedure if it proves effective. Currently, sonography is one of the best methods for monitoring the performance of lithotripsy. The authors have confirmed this. They have designed an in-vitro model which allows comparison between what is actually happening during gallstone lithotripsy and what is being seen by real-time sonography. The sonographic characteristics of the different phases of gallstone lithotripsy are presented.