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Biomedical subjects

E Passaro

Publications and source records attributed to E Passaro.

At least 73 records · Page 4Linked to original sources

Growth factors, oncogenes and the autocrine hypothesis.

Many aspects must be studied when considering theories of oncogenesis. Growth factors, the polypeptide hormones that are necessary for cell growth, and oncogenes, the genes that produce cancer, are only two aspects. Proto-oncogenes are found in normal cellular DNA and are believed to play regulatory roles in differentiation and development. Oncoviruses, mutation of DNA and chromosomal damage can activate proto-oncogenes and cause malignant change. Oncogenes can render transformed cells independent of growth factors. A cell can bypass the need for outside growth factors by producing the growth factor and its receptor, thereby using an autostimulatory impetus for growth. This is autocrine growth. An oncogene can also bypass the need for growth factors by activating or modifying growth factor receptors, or by stimulating intracellular events, such as tyrosine phosphorylation, both of which ultimately lead to cell division. The various mechanisms by which oncogenes act provide specific targets for treatment. Specific antigrowth factor or antireceptor antibodies or antagonists could interfere with autocrine regulation. Further research on the activation of oncogenes could provide valuable insight on regulation of the growth of tumors. Ultimately, the understanding of the molecular pathogenesis of cellular transformation will be a key to the prevention and treatment of cancer.

Cell Transformation, Neoplastic↗

Receptors.

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Humans↗

The amylase profile: a discriminant in biliary and pancreatic disease.

Serial serum amylase determinations were made in 85 consecutive patients who presented with an initially elevated value. In 35 patients (Group A), the clinical findings were consistent with biliary tract disease. All underwent cholecystectomy for documented cholelithiasis within a week of diagnosis, and 23 percent had choledocholithiasis as well. Fifty patients (Group B) presented with a first episode of acute alcoholic pancreatitis. An amylase profile, consisting of initial and final values and the daily rate of change, was significantly different between the two groups. The initial serum amylase value was higher in Group A patients and decreased more rapidly to a lower value than in Group B patients. We conclude that both the initial value and pattern of serum amylase decay distinguish the hyperamylasemia of biliary tract disease from that of alcoholic pancreatitis.

Acute Disease↗

Stricture of the common bile duct from chronic pancreatitis.

Early diagnosis and treatment of stricture of the common bile duct from chronic pancreatitis are essential as the life-threatening complications of biliary cirrhosis and acute cholangitis can occur even in the absence of clinical jaundice. In a series of 40 patients with longstanding chronic pancreatitis and stricture of the common bile duct, findings included chronic pain in 26 patients, jaundice in 17 patients, secondary biliary cirrhosis in six patients and acute cholangitis in six patients. Persistent elevation of the alkaline phosphatase level was the most sensitive laboratory indicator of occult obstruction of the biliary tract. The diagnostic long tapered stenosis of the distal common bile duct was delineated by percutaneous transhepatic cholangiography in 21 of 22 patients and endoscopic retrograde cholangiopancreatography in eight of 11 patients. Operative decompression of the biliary tract included 32 biliary-enteric bypasses, three sphincteroplasty procedures and three emergency tube drainages. There was one postoperative death and seven other patients had postoperative complications. Sphincteroplasty failed to relieve the obstruction in two patients and two patients with biliary-enteric bypass had late anastomotic strictures develop which required reoperation. Only seven patients were free of pain at follow-up study which ranged from 0.5 to 15.0 years. Clinical suspicion based upon persistent hyperaklalinphosphatemia, diagnosis by cholangiography and decompression of the biliary tract by choledochoenterostomy can reliably avert the lethal complications of stricture of the common bile duct caused by chronic pancreatitis.

Adult↗

The use of somatostatin and its analogs in the treatment of surgical disorders.

Somatostatin is a naturally occurring peptide with a wide spectrum of biologic actions, most of which are inhibitory in nature. It has wide distribution, and within the gastrointestinal tract is is found in the pancreas, the stomach, intestinal mucosa, and myenteric neurons. It appears to function as a classic circulating hormone, as well as both a paracrine or locally acting agent and a neurocrine agent. Because of its inhibitory actions on gut endocrine, secretory, and motor functions, it has potential applicability in the treatment of a variety of disorders of interest to the surgeon. Indeed, it has been used successfully in the management of upper gastrointestinal hemorrhage, secretory diarrhea, short bowel syndrome, pancreatitis, gastrointestinal fistulas, and peptide-secreting tumors of the gut (apudomas). This review discusses physiology, pathophysiology, and therapeutic applications of somatostatin that may be important in surgical practice.

Diarrhea↗

Delayed activation of tuberoinfundibular dopamine neurons and suppression of prolactin secretion in the rat after morphine administration.

The effect of morphine administration on the subsequent stimulation of prolactin (PRL) secretion and the release of dopamine from tuberoinfundibular neurons was examined in this study. The administration of morphine (15 mg/kg s.c.) resulted 4 hr later in suppressed serum PRL concentrations. In addition, the increase in serum PRL concentrations induced by restraint stress was attenuated greatly in rats treated 4 hr earlier with morphine. The morphine-induced attenuation of the PRL response to restraint stress was time-dependent and dose-related. The suppressive effect of morphine on PRL secretion was observed 3 to 6 hr after its administration and at doses of 10 to 20 mg/kg. A single injection of morphine also resulted 4 hr later in an attenuation of the PRL response to a second injection of morphine (7.5 mg/kg); however, the increase in serum PRL concentration produced by alpha-methyltyrosine (250 mg/kg) was unaltered by prior morphine administration. The suppressive effect of morphine on PRL secretion was not observed in rats treated with the opiate antagonist naloxone (2.5 mg/kg). Associated with the delayed suppressive effect of morphine on serum PRL concentrations was a delayed increase in the concentration of dopamine in hypophysial portal plasma and an increase in the turnover of dopamine in the median eminence. The morphine-induced stimulation of the release of dopamine into hypophyseal portal blood was attenuated significantly in animals treated with naltrexone (1 mg/kg). It is concluded that morphine exerts a biphasic effect on both the secretion of PRL and the release of dopamine from tuberoinfundibular neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Benign and malignant gastrinoma.

The advent of the histamine H2-receptor antagonists and the renewed interest in curative surgery in patients with gastrinoma have made the differentiation between benign and malignant tumors of critical importance. An analysis of 65 patients with gastrinoma followed for an average of 93 months revealed two distinct clinical groups: those with and those without hepatic tumors at initial examination or operation. Among the 14 patients with hepatic tumors, 12 had multiple liver metastases from pancreatic or duodenal primary tumors, and 2 had primary hepatic gastrinomas. Ten of the 14 patients (71 percent) died from tumor progression, and the total tumor-related mortality for this group was 79 percent. In contrast, only 1 of 15 patients (7 percent) with tumor in the lymph nodes died from a tumor-related cause (recurrent ulcer hemorrhage), and none died from tumor progression. Only a single patient with lymph node metastases at initial exploration went on to the development of liver metastases, which was found incidentally at autopsy 313 months later. Among 23 patients with either primary tumors only or no tumors found at laparotomy, there was only one tumor-related death and no deaths from tumor spread. Life-table analysis demonstrated a significantly decreased length of survival for patients with liver tumor compared with those without liver involvement. Multiple endocrine adenopathy syndrome was not a significant factor in survival. Serum gastrin levels were likewise nondiscriminatory. Six of 52 patients (12 percent), including three with tumor in the lymph nodes, were apparently cured by excision of all gastrinoma recognized at laparotomy. The cure rate was 23 percent for patients without multiple endocrine adenopathy syndrome or liver metastases. Hepatic metastases is a definitive marker for clinically malignant disease and portends a poor prognosis. Patients with gastrinoma confined to the lymph nodes uncommonly follow a malignant clinical course. Such patients have at least a 20 percent probability of surgical cure if they do not have multiple endocrine adenopathy syndrome.

Adult↗

Influence of cisternal pressure on passage of neuropeptides from the cerebrospinal fluid into the peripheral circulation.

Passage of neuropeptides from the cerebrospinal fluid to circulation depends upon cisternal pressure. When cisternal collecting pressure was kept at -20 cm, plasma levels of gastrin-17 and somatostatin-14 remained at basal values despite perfusion of high doses of the peptides into the cerebro-ventricular system. Progressive reduction of this pressure above -15 cm results in a progressive rise of the peripheral concentration of the peptides. Discrimination between central and peripheral action of centrally administered neuropeptides is, therefore, possible.

Animals↗

The gastrinoma triangle: operative implications.

Operative experience with 45 gastrinoma patients has led to the identification of an anatomic area where occult tumors can be discovered and where excision of these tumors had led to apparent cure. Of 36 patients with histologically confirmed gastrinomas, 27 patients (75 percent) had obvious and 9 patients (25 percent) had occult tumors. All nine occult lesions were found within an anatomic triangle defined by the junction of the cystic and common bile ducts superiorly, the junction of the second and third portions of the duodenum inferiorly, and the junction of the neck and body of the pancreas medially. Although occult tumors from three patients (in the lymph nodes in two patients and in the duodenum in one patient) were removed primarily for histologic diagnosis, postoperative serum gastrin levels have remained within the normal range (follow-up of 86 to 99 months). Two patients had excision of the tumor with intent to cure. One patient with a solitary duodenal tumor was apparently cured but committed suicide 3 months postoperatively. The other patient had both obvious primary and occult metastatic tumors within the triangle and was eugastrinemic 9 months after excision. In all patients in whom tumor was found, it was locally excised, and no patient was subjected to radical pancreatic resection. There were no postoperative complications related to tumor removal. An aggressive approach towards curative tumor excision is now advocated for all gastrinoma patients who are suitable operative risks and have no evidence preoperatively of liver metastases or the multiple endocrine neoplasm-type I syndrome.

Biopsy↗

Cholecystokinin acts through catecholaminergic mechanisms in the hypothalamus to influence ingestive behaviour in the rat.

Administration of cholecystokinin (CCK) (0.2 - 0.6 micrograms in a volume of 2 microliter) into the lateral cerebral ventricle caused a decrease in intake of food but a relative increase in intake of water (or water-to-food ratio) in rats. To determine whether the anorexic actions of CCK were mediated through the hypothalamic nuclei, rats were infused with CCK (0.02 - 0.12 microgram in a volume of 0.5 microliter) through previously implanted hypothalamic cannulae. Administration of CCK into the lateral hypothalamus, but not the anterior hypothalamus or ventromedial hypothalamus, caused decreased intake of food and a relative increased intake of water. In addition, the responses induced by injection of CCK into the hypothalamus were completely abolished by selective depletion of catecholamines in the hypothalamus (eg. noradrenaline and dopamine) with intra-hypothalamic injection of 6-hydroxydopamine. Intraperitoneal administration of 0.12 microgram of CCK had no effect on the intake of food and water in rats. The data indicate that CCK acts through catecholaminergic mechanisms in the hypothalamus to influence feeding behaviour.

Animals↗

Effect of two dopamine agonists, TL-99 and 3-PPP, on prolactin secretion in the rat.

TL-99 and 3-PPP, two putative dopamine autoreceptor agonists, effectively suppressed serum prolactin (PRL) concentrations in rats treated with alpha-methyltyrosine. In addition, the secretion of PRL from anterior pituitary tissue under in vitro conditions was significantly inhibited by TL-99 and 3-PPP. These findings are supportive of the view that TL-99 and 3-PPP exert a dopamine agonist action at dopamine receptors in the anterior pituitary gland.

Animals↗