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Biomedical subjects

M Ebert

Publications and source records attributed to M Ebert.

At least 55 records · Page 3Linked to original sources

Carcinoid of the ampulla of Vater. Clinical characteristics and morphologic features.

BACKGROUND: Carcinoid tumors of the gastrointestinal tract are most common localized in the appendix, followed by the small intestine, the rectum, and the stomach. The localization of these tumors at the ampulla of Vater is extremely seldom. METHODS: In the present study the authors describe two patients with carcinoid tumors of the ampulla Vater and review 71 previously published cases. RESULTS: Most patients presented with jaundice, but without carcinoid syndrome. Because the tumor grows submucosally, preoperative diagnosis was correct only in 15%. Most tumors were around 2 cm in size. Metastasis to lymph nodes and/or liver was present in 45%. Standard treatment is Whipple resection or local excision in small tumors. CONCLUSIONS: Carcinoid tumors of the ampulla of Vater are an extremely rare clinical entity. Generally, the prognosis is good with a 5-year survival period of 90%.

Adult↗

Inhibition of pancreatic secretion under long-term octreotide treatment in humans.

The somatostatin analogue octreotide (SMS 201-995) is a potent inhibitor of human exocrine pancreatic secretion. In the present study we analyzed the effect of octreotide (3 x 100 micrograms, daily) given over a time period of 7 days on hormone-stimulated exocrine pancreatic secretion in 6 healthy volunteers using a secretin-ceruletide test. The secretin-ceruletide test was carried out before, following the first injection of octreotide (day 1) and after a 7-day treatment with 3 x 100 micrograms octreotide daily. Duodenal fluid was collected over 30 min without stimulation, over 60 min following a bolus injection of 1 U/kg body weight secretin, and over 60 min during a continuous infusion of secretin and ceruletide. Following the first injection of octreotide and following 7 days of octreotide treatment secretin/ceruletide-stimulated amylase secretion was significantly reduced. Trypsin and chymotrypsin secretion was significantly reduced after the first injection of octreotide when pancreatic secretion was stimulated by secretin and ceruletide simultaneously. However, secretin and ceruletide-induced trypsin and chymotrypsin secretion was not inhibited after 7 days of octreotide treatment. Baseline, secretin and secretin/ceruletide-stimulated bicarbonate output were not influenced by octreotide either following the first injection of octreotide or the 7 days' treatment. Octreotide is a potent inhibitor of secretin/ceruletide-stimulated pancreatic amylase, trypsin and chymotrypsin secretion. However, following a 7-day treatment with octreotide this inhibition is only persistent for pancreatic amylase secretion.

Adult↗

Role of octreotide in the treatment of pancreatic cancer.

Prognosis in patients with advanced pancreatic cancer is dismal. There has been no effective therapy for these patients so far. Somatostatin and its analogues have been proven to be potent inhibitors of experimental pancreatic cancer. Tumor inhibition is supposed to be mediated directly by somatostatin-binding sites or indirectly by suppression of growth factors. In two trials the value of the new somatostatin analogue octreotide in a low-dose (3 x 100 micrograms/day) and a high-dose (3 x 2,000 micrograms/day) protocol was evaluated in patients with advanced pancreatic cancer. Median survival of the patients with a low-dose protocol was 3 months. However, the treatment of pancreatic cancer with a high-dose protocol revealed a median survival of 6 months and stable disease in 4/10 patients. According to quality of life scoring 4 patients showed values comparable to healthy controls. Octreotide therapy with a high-dose protocol is a promising experimental therapeutic approach to advanced pancreatic cancer.

Female↗

Portal films for relative exit dose determinations.

Portal films are radiographic images taken regularly in external photon beam radiotherapy in order to verify geometrical set-up. However, they also contain quantitative dose information. Absolute dosimetry with film is possible but the desired accuracy of +/- 5% is difficult to achieve. However, relative dosimetry with film would be useful in combination with a point determination of absolute dose, though a dose response linearisation is required for relative dosimetry over the range of doses given to portal films in routine clinical practice. For this purpose, a technique for the rapid dose response linearisation of portal films is investigated in simulated treatment situations and evaluated in terms of the ability to yield relative exit dose distributions from the portal films. A combination of such distributions with a single determination of radiation transmission with diodes should generate full two-dimensional transmission information. Distributions obtained from two anthropomorphic phantoms provided results consistent with distributions obtained from a treatment planning system to generally within +/- 5%, and most often within +/- 2%. It is concluded that the extraction of exit dose information from portal films would be useful for mantle, compensated, or other unusual treatment situations.

Calibration↗

Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival.

BACKGROUND: Transforming growth factor beta s (TGF-beta s) constitute a family of bifunctional polypeptide growth factors that either inhibit or stimulate cell proliferation. Perturbations in TGF-beta expression and function may lead to loss of negative constraints on cell growth. In this study, we examined TGF-beta expression in human pancreatic cancer. METHODS: The distribution of TGF-beta isoforms in 60 human pancreatic cancers was examined using immunohistochemical, Northern blot, and in situ hybridization techniques. RESULTS: Immunohistochemical analysis showed the presence of TGF-beta 1 (47% of tumors), TGF-beta 2 (42% of tumors), and TGF-beta 3 (40% of tumors) in the cancer cells. The presence of TGF-beta 2 was associated with advanced tumor stage (P < 0.05). Furthermore, there was a significant correlation between the absence of TGF-beta s in the tumors and longer postoperative survival. Northern blot analysis indicated that, by comparison with the normal pancreas, pancreatic adenocarcinomas showed 11- (P < 0.001), 7- (P < 0.05), and 9-fold (P < 0.001) increases in the messenger RNA (mRNA) levels encoding TGF-beta 1, TGF-beta 2, and TGF-beta 3, respectively. By in situ hybridization, these mRNA moieties colocalized with their respective proteins in the cancer cells. CONCLUSIONS: These findings show that human pancreatic cancers show increased levels of TGF-beta isoforms and enhanced TGF-beta mRNA expression and suggest that the presence of TGF-beta s in pancreatic cancer cells may contribute to disease progression.

Adenocarcinoma↗

Enzyme treatment after gastrointestinal surgery.

After gastrointestinal surgery, patients often suffer from maldigestion. The extent of this maldigestion syndrome depends on the type of surgical procedure performed. After total pancreatectomy, subtotal left resection, resection for chronic pancreatitis. Whipple operation with ductal occlusion, and total gastrectomy, patients need obligatory enzyme treatment. After partial pancreatectomy without duct occlusion or partial gastrectomy, enzyme treatment should be initiated when exocrine pancreatic insufficiency occurs.

Chronic Disease↗

[Surgery in chronic pancreatitis. II. Late results following non-resection operations].

Between 1966 and 1985, 994 patients with chronic pancreatitis were treated at a University Surgical Department, 346 by drainage or diversion procedure, 339 by resection and 309 conservatively. The most frequent non-resecting procedures were: pancreatic pseudocyst drainage in 146, biliary-digestive tract anastomosis in 80, gastro-enterostomy in 15, biliary-tract revision in 58 and pancreatic duct drainage in 7 patients. More than half the patients had previously been operated on at least once. Overall postoperative death rate was 6.6%. Of those operated on up to 1983, whose subsequent course was analysed retrospectively, 16% had died (mean observation period 4.6 years). As many as 29% of patients had further bouts of pancreatitis. Weight remained steady or increased in 82%, the number of those with diabetes increased by 6%. All but 12% remained free of pain postoperatively or had only minor and occasional symptoms. Alcohol abuse decreased markedly. If alcohol consumption remained moderate (less than 50 g daily), late mortality rate was definitely decreased. Drainage or diversion procedures and pancreas resection are not competitive but complementary methods in chronic pancreatitis. Imaging techniques have helped the trend towards more conservative management.

Adolescent↗

Abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa. Pathophysiologic mechanisms in underweight and weight-corrected patients.

To study the pathophysiology of hypercortisolism in patients with anorexia nervosa, we examined plasma ACTH and cortisol responses to ovine corticotropin-releasing hormone before and after correction of weight loss. We also studied patients with bulimia whose weight was normal, since this disorder has been suspected to be a variant of anorexia nervosa. Before their weight loss was corrected, the anorexic patients had marked hypercortisolism but normal basal plasma ACTH. The hypercortisolism was associated with a marked reduction in the plasma ACTH response to corticotropin-releasing hormone. When these patients were studied three to four weeks after their body weight had been restored to normal, the hypercortisolism had resolved but the abnormal response to corticotropin-releasing hormone remained unchanged. On the other hand, at least six months after correction of weight loss their responses were normal. The bulimic patients whose weight was normal also had a normal response to corticotropin-releasing hormone. We conclude that in underweight anorexics, the pituitary responds appropriately to corticotropin-releasing hormone, being restrained in its response by the elevated levels of cortisol. This suggests that hypercortisolism in anorexics reflects a defect at or above the hypothalamus. The return to eucortisolism soon after correction of the weight loss indicates resolution of this central defect despite persistence of abnormalities in adrenal function.

Adrenocorticotropic Hormone↗

Genetic brain polypeptide variants in inbred mice and in mouse strains with high and low sensitivity to alcohol.

Twelve genetically determined brain polypeptide charge variants were identified by comparing cerebellar vermis of 7 inbred mouse strains and of mice selectively bred from 8 strains closely related to these 7 ancestral strains and one other for acute behavioral sensitivity to the sedative effects of ethanol. The selectively bred ethanol-sensitive (LS, long sleep) and insensitive (SS, short sleep) mice exhibited different allelic variants at 6 of these 12 gene loci expressed in the cerebellum. Variant polypeptide A1 (81 kdalton, pI 5.6) was shown to be associated with the membrane of synaptosomal mitochondria and to exhibit a basic variant in SS mice that is determined by a dominant allele. Other variant polypeptides showed codominant inheritance in F1 crosses. However, the phenotype of no single one of these brain polypeptides consistently correlated with the ethanol behavioral sensitivity of the 7 inbred mouse strains nor of 8 recombinant inbred (B X D, C57BL X DBA) strains. This finding supports the hypothesis that a substantial amount of inbreeding, leading to random fixation of alleles independent of selection for ethanol sensitivity, occurred during the breeding of the SS and LS mice. The present findings of a lack of a strong association between sleep time and a brain polypeptide variant do not preclude the existence of a major gene effect contributing to variation in acute sensitivity to ethanol but are consistent with reports that multiple loci are responsible for the difference in ethanol sensitivity between SS and LS mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Clinical findings in patients with anorexia nervosa and affective illness in their relatives.

The most prevalent psychiatric disorders in the families of patients with anorexia nervosa are bipolar and unipolar major affective disorder. The presence of affective disorder, self-induced vomiting, or bulimia in the patient is not predictive of affective illness in the relatives. Thus these features do not define genetic heterogeneity within anorexia nervosa. There may be genetic factors shared between anorexia nervosa and affective disorders.

Adult↗

Abnormalities in plasma and cerebrospinal-fluid arginine vasopressin in patients with anorexia nervosa.

Previous studies have indicated that many patients with anorexia nervosa have defects in urinary concentration or dilution suggestive of abnormal secretion of the antidiuretic hormone arginine vasopressin. To explore this possibility, we examined the response of plasma vasopressin to intravenous hypertonic saline in anorexic patients before and after correction of their weight loss. We also measured basal levels of the hormone in the cerebrospinal fluid. In all four subjects studied before correction of weight loss, the response to hypertonic saline was abnormal: in one, the plasma level of arginine vasopressin increased subnormally relative to the plasma sodium level; in the other three, it fluctuated erratically, with no relation to plasma sodium. These defects persisted in the three patients studied three to four weeks after recovery of body weight. In two patients who were initially studied when they were underweight, the defects were gone six months after recovery; in five of seven other patients studied at least six months after recovery but not while they were underweight, the response was normal. Abnormalities in the osmoregulation of plasma arginine vasopressin were not accounted for by nonosmotic stimuli and were almost always associated with an absolute increase in the level of arginine vasopressin in the cerebrospinal fluid or a reversal of the normal (less than 1.0) cerebrospinal fluid/plasma ratio of arginine vasopressin. These results indicate that most if not all patients with anorexia nervosa have abnormal levels of arginine vasopressin in their plasma and cerebrospinal fluid that are corrected very slowly with weight gain. The cause and consequences of these abnormalities remain to be determined.

Adult↗

A family with histologically confirmed Alzheimer's disease.

A Canadian family comprising 51 members affected with Alzheimer's disease was evaluated clinically, histologically, and genetically. Ancestors were traced through eight generations, and 51 members were examined at the National Institute of Mental Health, Bethesda, Md. The pedigree is consistent with autosomal dominant inheritance. The effect of interrelatedness among some parents of affected individuals is unknown. In contrast to other studies, there was not an increased incidence of Down's syndrome, hematologic malignancy, or preponderance of affected females.

Alzheimer Disease↗

Intellect, perceptual characteristics, and weight gain in anorexia nervosa.

Studied weight gain in a group of primary anorexics by examining two popular psychodiagnostic measures, the Wechsler and Rorschach, for indices that may predict improvement. Twenty-seven successively admitted anorexics to a behavior modification weight gain program at NIMH were studied. Using weight gain as a continuous criterion, multiple regression analyses indicated that perceptual-personality variables did not have any predictive power. Cognitive focusing skills, as measured by the Arithmetic and Digit Span subtests of the Wechsler, were found to account for roughly half of the variance and to be good predictors of weight gain.

Adult↗

Disturbances of sleep and cognitive functioning in patients with dementia.

The relationship of sleep, circadian rhythms, and cognitive impairment in dementia patients is briefly reviewed. All-night sleep EEG data were collected in relatively young and relatively unimpaired patients with presumptive Alzheimer's disease and eight age-matched controls. Delta sleep time and Delta sleep % (Stages 3 and 4)--but not REM sleep measures--were significantly reduced in the patients. Implications of these findings are discussed.

Aged↗

Behavioral, biochemical and neuroendocrine responses to amphetamine in normal twins and 'well-state' bipolar patients.

An i.v. injection of dextroamphetamine (0.3 mgm/kg) was given to 13 pairs of normal monozygotic twins, three pairs of normal dizygotic twins and 11 patients with bipolar affective disorder in remission and off medications. Behavioral excitation in response to amphetamine was highly correlated in monozygotic twins; it was predicted by the baseline variables of high plasma MHPG, low serum prolactin and low pulse; it correlated with a rise in cortisol; and it was not correlated with plasma amphetamine level. Pre-infusion baseline MHPG and growth hormone and prolactin responses to amphetamine also were concordant in twins. Plasma amphetamine level, pulse and blood pressure and cortisol responses were not concordant, suggesting significant environmental influences. Haloperidol pretreatment in one pair of twins abolished the excitation response but did not reduce increases in cortisol and growth hormone. This suggests a role for dopamine in the excitation response but predominant serotonergic and noradrenergic mediation of the hormonal responses. None of the responses or baseline measures distinguished patients from controls. Thus, no consistently altered sensitivity to monoaminergic stimulation by amphetamine in bipolar affective disorder was demonstrated in this study. This is one of the first reports of familial (possibly genetic) variation in a psychostimulant drug response in man. The responses identified as concordant may be useful in characterizing other pathologic conditions.

Adolescent↗

[Massive osteolysis (Gorham-Stout's syndrome) with local neurofibromatosis (author's transl)].

The rare condition of massive osteolysis is illustrated by a 75-year-old man with involvement of the right arm which began at the age of 16. Serial radiographs over a period of 33 years are compared. In addition to the typical haemangiomatous vascular proliferation and connective tissue growth in the affected bone, there were also changes in the peripheral nerves, such as neurinomas and neurofibromas, which have not been previously described. Arteriography is usually not able to demonstrate the angiomatous tissue, but this was convincingly seen by means of sequential scintigraphy (99mTc-MDP). This finding, with absence of uptake on a subsequent bone scan, may be regarded as the typical isotope finding in massive osteolysis.

Aged↗