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Biomedical subjects

S M Graham

Publications and source records attributed to S M Graham.

At least 19 recordsLinked to original sources
PubMed1992

Isoprenoid addition to Ras protein is the critical modification for its membrane association and transforming activity.

We have introduced a variety of amino acid substitutions into carboxyl-terminal CA1A2X sequence (C = cysteine; A = aliphatic; X = any amino acid) of the oncogenic [Val12]Ki-Ras4B protein to identify the amino acids that permit Ras processing (isoprenylation, proteolysis, and carboxyl methylation), membrane association, and transformation in cultured mammalian cells. While all substitutions were tolerated at the A1 position, substitutions at A2 and X reduced transforming activity. The A2 residue was important for both isoprenylation and AAX proteolysis, whereas the X residue dictated the extent and specificity of isoprenoid modification only. Differences were observed between Ras processing in living cells and farnesylation efficiency in a cell-free system. Finally, one farnesylated mutant did not undergo either proteolysis or carboxyl methylation but still displayed efficient membrane association (approximately 50%) and transforming activity, indicating that farnesylation alone can support Ras transforming activity. Since both farnesylation and carboxyl methylation are critical for yeast a-factor biological activity, the three CAAX-signaled modifications may have different contributions to the function of different CAAX-containing proteins.

3T3 Cells↗
PubMed1992

Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants.

A review of the clinical findings in six infants with nutritional vitamin B12 deficiency seen during the last 10 years was undertaken and an attempt made to obtain long-term neurologic follow-up. There was a consistent clinical pattern in vitamin B12-deficient infants; irritability, anorexia, and failure to thrive were associated with marked developmental regression and poor brain growth. Two of the four patients who qualified for long-term review had a poor intellectual outcome. Although early response to treatment is satisfying, the long-term consequences of nutritional vitamin B12 deficiency in infants emphasize the need for prevention or early recognition of this syndrome.

Anemia, Pernicious↗
PubMed1992

Laparoscopic cholangiography. Results and indications.

One hundred sixty-five operative cholangiograms were attempted in 364 patients who underwent laparoscopic cholecystectomy (45%). Laparoscopic cholangiography was successful in 150 of 165 attempts (91%). Eighty-nine per cent of studies were normal (134/150) and 11% were abnormal (16/150). All 134 patients with normal cholangiograms remained asymptomatic (false-negative rate, 0%). False-positive studies occurred in 3 of 150 (2%) total cholangiograms and 3 of 12 (25%) abnormal cholangiograms consistent with choledocholithiasis. A total of 16 of 364 patients had proven common bile duct stones (4.4%). Eight of the sixteen stones were removed by preoperative endoscopic retrograde cholangiopancreatography/sphincterotomy. Five of sixteen stones were found at cholangiography, four of which were unsuspected (4/150, 2.6%). Retained common duct stones were found in 3 of 214 patients not undergoing cholangiography (1.4%). No complications or deaths occurred that were due to cholangiography. One biliary injury occurred (1/364, 0.3%), in a patient with aberrant anatomy who did not undergo cholangiography. Laparoscopic cholangiography is a safe technique with a success rate greater than 90%. Routine cholangiography is presently recommended for prevention of biliary injury, detection of stones in the cystic and common ducts, and for training purposes, especially during the learning phase of laparoscopic cholecystectomy.

Cholangiography↗
PubMed1992

Gastrocolic and duodenocolic fistulas in Crohn's disease.

Crohn's disease is a rare cause of gastrocolic and duodenocolic fistulas. Only 83 examples (27 gastric, 52 duodenal, four both) have been described. Weight loss, abdominal pain, and diarrhea are common features but fail to distinguish a fistula from active inflammatory bowel disease. Fecal vomiting is pathognomic but is present in one third of gastrocolic and only 2% of duodenocolic fistulas. Diagnosis is most readily made by contrast radiography, with barium enema being more sensitive than barium meal. Although several gastrocolic fistulas have been successfully treated with long-term 6-mercaptopurine, surgery is the mainstay of therapy. An isolated duodenocolic fistula should not be regarded as the primary indication for operation because most are asymptomatic. Ileocolonic resection with simple gastric or duodenal repair is safe and effective in most cases. An ileocolonic anastomosis should be positioned away from the stomach or duodenum or protected with omentum to prevent recurrent fistulization. A number of fistulas appear to have arisen from gastric or duodenal Crohn's, but the vast majority originate from diseased colon.

Adult↗
PubMed1992

Laparoscopic general surgery: current status and future prospects.

The capability of performing major abdominal surgery while avoiding a large abdominal incision has clear benefits for patient care. Laparoscopic cholecystectomy can reduce hospital stays and the length of the recovery period, as well as decrease postoperative pain, diminish scarring, and provide significant cost savings.

Cholecystectomy↗
PubMed1991

Laparoscopic cholecystectomy. Experience with 375 consecutive patients.

Three hundred seventy-five consecutive patients underwent laparoscopic cholecystectomy from September 1989 to January 1991. Three hundred forty-one (91%) presented on an elective basis, and the remaining 34 patients (9%) were admitted for acute cholecystitis (24), gallstone pancreatitis (9), and cholangitis (1). Of the 375 patients, 20 were converted to laparotomy and cholecystectomy, for an overall success rate of 95% for patients undergoing laparoscopic cholecystectomy. Three hundred nineteen patients (90%) were discharged within 24 hours of surgery. Operative cholangiography was completed in 141 patients, showing choledocholithiasis in five (managed by postoperative endoscopic retrograde cholangiopancreatography [ERCP] in 4, common bile duct exploration [CBDE] in 1). Two retained stones (0.9%) were detected in 214 patients not undergoing cholangiography. Three patients (0.8%) were reoperated on because of perioperative complications. Overall morbidity for patients undergoing laparoscopic cholecystectomy was 3.5%. Major complications (0.6%) included a single common hepatic duct injury and a delayed cystic duct leak at 10 days. Minor complications occurred in 11 patients (2.9%). The single perioperative death (0.3%) was due to a myocardial infarction on postoperative day 3, after an otherwise uncomplicated laparoscopic procedure. Laparoscopic cholecystectomy appears to offer significant advantages to patient recovery, and these data suggest that it can be performed with an efficacy, morbidity rate, and mortality rate similar to those of open cholecystectomy.

Adolescent↗
PubMed1991

Combined laparoscopic cholecystectomy and selective vagotomy.

Laparoscopic surgery offers distinct advantages to traditional surgery, including decreased hospitalization and recovery periods, decreased postoperative discomfort, and improved cosmesis. A feasible laparoscopic approach to the treatment of peptic ulcer disease might confer similar patient benefits. A modified highly selective vagotomy (in combination with cholecystectomy for symptomatic cholelithiasis) has been successfully completed under laparoscopic guidance in a patient with intractable ulcer disease. The patient was discharged on the second postoperative day, tolerating a regular diet. The patient's dyspeptic symptoms disappeared during the immediate postoperative period and further endoscopic evaluation revealed resolution of active ulcer disease. Although experience is still limited in the United States, initial clinical results from Europe would indicate that laparoscopic vagotomy is not only feasible but effective. With further experience, laparoscopic vagotomy may provide a viable alternative to the standard treatment of peptic ulcer disease.

Cholecystectomy, Laparoscopic↗
PubMed1990

Collaboration to facilitate baccalaureate education in emergency departments.

The use of emergency departments for baccalaureate nursing education has proved to be a rewarding experience for students, emergency department (ED) staff, and nursing school faculty. The primary factor for the success of this experience was the collaborative interaction of ED nursing personnel, and school of nursing faculty in designing the educational experience. ED staff complemented the faculty role and facilitated clinical experiences for the nursing students. This article identifies various teaching principles and strategies ED staff used to create a successful clinical experience for baccalaureate nursing students.

Curriculum↗
PubMed1989

Cholecystokinin augmentation of 'surgical' pancreatitis. Benefits of receptor blockade.

The management of acute pancreatitis has not changed appreciably throughout several decades. Recent evidence has suggested that cholecystokinin (CCK) may play an important role in pancreatic disease. Investigations into the precise role of CCK in acute pancreatitis have been hampered by the lack of a specific CCK receptor antagonist. Using a newly described, highly potent and specific CCK receptor antagonist, L-364,718, the effect of CCK in two models of acute "surgical" pancreatitis was examined: (1) the bile salt ductal perfusion model in the rat and (2) a traumatic model in the guinea pig. At a suboptimal dose for pancreatic enzyme secretion (25 pmol/kg/h), CCK was found to potentiate the severity of the ensuing pancreatitis in both models. Continuous CCK receptor blockade with L-364,718 (25 nmol/kg/h) improved biochemical, morphologic, and survival indexes. This study suggests that physiologic levels of CCK play an important permissive role in the evolution of acute pancreatitis. The use of L-364,718 as an investigative probe or therapeutic tool for acute pancreatitis is worthy of further consideration.

Acute Disease↗
PubMed1988

Bleeding colonic ulcers secondary to atheromatous microemboli after left heart catheterization.

Atheromicroembolism after aortic or cardiac catheterization is frequently found at autopsy but rarely recognized in life, perhaps because many cases are asymptomatic. We report two patients who, after left heart catheterization, developed gastrointestinal hemorrhage from a solitary colonic ulcer caused by occlusive atheromicroemboli in submucosal vessels. We briefly review the spectrum and pathogenesis of atheromicroembolic injury to the gastrointestinal tract. Atheromicroemboli, which occlude vessels too small to be visualized by angiography, should be considered in the differential diagnosis of gastrointestinal bleeding in patients who have undergone aortic instrumentation.

Aged↗
PubMed1988

Cholangitis glandularis proliferans. A histologic variant of primary sclerosing cholangitis with distinctive clinical and pathological features.

This is the first report in the American literature of a recently described histologic variant of primary sclerosing cholangitis (PSC). Only six examples of this unique entity, called cholangitis glandularis proliferans (CGP), or proliferative cholangitis, have previously been reported. This disorder typically presents as painless jaundice but differs clinically from PSC by occurring predominantly in females and lacking an association with inflammatory bowel disease. The unique histological features are characterized by florid intramural proliferation of glandular elements in addition to an intense inflammatory component. Anatomically, the lesion is confined to the extrahepatic biliary tree, which enables its successful surgical extirpation since it does not appear to be progressive.

Adult↗
PubMed1987

Cecal diverticulitis. A review of the American experience.

The etiology of cecal diverticulitis remains unclear. The majority of diverticula are solitary and probably false and may be the result of the same degenerative process seen in the more common left-sided diverticulosis. A minority are true diverticula and may be of congenital origin. Cecal diverticulitis is clinically indistinguishable from acute appendicitis although patients with cecal diverticulitis tend to be older (average age, 40 years), have a longer duration of symptoms, and present less often with nausea and vomiting. In patients with previous appendectomy and in those with more indolent symptoms, barium enema may be helpful in making the diagnosis. If nonoperative treatment is chosen, careful follow-up with air contrast barium enema and colonoscopy should be carried out. The majority of patients require surgery and two types of cecal diverticulitis are encountered at laparotomy. The usual type, accounting for two thirds of cases, is easy to recognize, has an inflamed projection from the cecal wall, and is dealt with by a limited local diverticulectomy. Some authors advocate nonsurgical treatment for this first group of patients. Incidental appendectomy is advocated to avoid confusion should symptoms occur postoperatively. The hidden variant presents as a large, indurated phlegmon and is difficult to distinguish from a perforated cecal carcinoma. With the hidden variant, right hemicolectomy is the surgical treatment of choice and carries a 1.4 percent mortality.

Cecal Diseases↗
PubMed1987

Superior mesenteric artery syndrome following ileal J-pouch anal anastomosis. An iatrogenic cause of early postoperative obstruction.

This is the first case report of the superior mesenteric artery syndrome developing in a patient following total proctocolectomy and ileal J-pouch anal anastomosis. In addition, this is the first demonstration of this syndrome using abdominal CT scan. A 22-year-old veteran underwent total proctocolectomy for left-sided ulcerative colitis because of failure of medical therapy. At operation an ileal J-pouch anal anastomosis was constructed. Following operation, the patient developed an intestinal obstruction. Abdominal CT scan demonstrated scant retroperitoneal fatty tissue, massive dilatation of the duodenum proximal to the midline, and tapered narrowing of the duodenum between the superior mesenteric artery and aorta. These findings indicated superior mesenteric artery syndrome: arteriomesenteric obstruction of the duodenum. Based on the experience of this case, the authors believe that compression of the duodenum by the superior mesenteric artery may be a common but unsuspected cause of prolonged postoperative ileus or early postoperative obstruction following ileal pouch anal anastomosis.

Adult↗
PubMed1987

Provocative testing for occult medullary carcinoma of the thyroid: findings in seven children with multiple endocrine neoplasia type IIa.

A rise in the serum calcitonin (CT) following provocative testing has facilitated making the diagnosis of occult medullary carcinoma of the thyroid (MCT) or C cell hyperplasia (CCH) in asymptomatic children of kindred with multiple endocrine neoplasia (MEN) type IIa. Findings were reviewed for seven children varying in age from 3 to 16 years screened at our institution between 1976 and 1986. Three had elevated basal calcitonin (S-CT). Six had significant elevation of calcitonin (delta-CT) after stimulation. Total thyroidectomy was performed in all seven. Five had MCT with bilobar involvement in three. CCH was present in all five. Two patients had no gross, microscopic, or immunohistochemical evidence of MCT or CCH. One of three had an elevated S-CT. The other had a significant delta-CT. All patients have normal postoperative S-CT and delta-CT. Our experience indicates the importance of beginning stimulation tests of affected kindred at less than 3 years of age. It appears, however, that neither elevated S-CT or positive delta-CT are perfect predictors of parafollicular cell pathology. Solitary parathyroid enlargement, second thyroid malignancy, and branchial pouch anomalies may occur with MEN IIa. One patient with MCT had a focus of papillary carcinoma. One patient with primary hyperparathyroidism had a solitary enlarged parathyroid adenoma. Additional findings were the presence of nodules of ectopic thymus in close association with the thyroid gland in three patients.

Adolescent↗
PubMed1987

Age-associated alterations in hepatic beta-adrenergic receptor/adenylate cyclase complex.

The effect of age on catecholamine regulation of hepatic glycogenolysis and on hepatic adenylate cyclase was studied in male rats up to 24 mo of age. Epinephrine and norepinephrine stimulated glycogenolysis in isolated hepatocytes at all age groups studied. Isoproterenol, however, stimulated glycogenolysis only at 24 mo. In isolated liver membranes, usual activators of adenylate cyclase increased the activity of the enzyme considerably more in membranes from 24-mo-old rats than in membranes from either 3- or 21-mo-old rats. The Mn2+-dependent activity of the cyclase was increased by 2.9-fold in 3-mo-old animals and approximately 5.7-fold in 24-mo-old rats, indicating a substantial age-dependent increase in the intrinsic activity of the catalytic unit. The density of the beta-adrenergic receptor, as measured by the binding of [125I]-iodocyanopindolol to plasma membranes, was 5-8 fmol/mg protein in rats aged 3-12 mo but increased to 19 fmol/mg protein in 24-mo-old rats. Computer-aided analysis of isoproterenol competition of the binding indicated a small age-dependent increase (from 30% at 3 mo to 43% at 24 mo) in the proportion of beta-receptors in the high-affinity state. These observations suggest that beta-receptor-mediated hepatic glycogenolysis in the aged rat is predicated upon increases in the density of beta-receptors as well as increased intrinsic activity of the catalytic unit of adenylate cyclase.

Adenylyl Cyclases↗