ErbB2 growth factor receptor, a marker for neuroendocrine cells?

BACKGROUND/AIMS: The overexpression of ErbB2 in pancreatic cancer has been reported with a varying incidence ranging between 1 and 80%. Our routine examination, however, revealed a consistently strong immunoreactivity of three anti-ErbB2 growth factor receptor antibodies in pancreatic islets and intrapancreatic ganglia. To validate our findings and to understand the reasons for the reported differences in the frequency of ErbB2 overexpression in pancreatic cancer, the following studies were performed. MATERIALS AND METHODS: Tissue samples from 12 normal pancreata, 7 surgical chronic pancreatitis cases, 21 primary pancreatic adenocarcinomas, 9 metastatic pancreatic adenocarcinomas, and 4 islet cell tumors were subjected to immunohistochemical examination using antibodies from three manufacturers. Cultured human islet cells and pancreatic cancer cell lines, as well as samples from the gastrointestinal tract, the CNS, and the adrenal gland were included in the study. For comparison, mammary cancer tissue and mammary cancer cells, as well as selected tissues from Syrian golden hamsters, were used. To verify the results, Western blot and Northern slot-blot analyses were performed. RESULTS: Pancreatic cancer cells, in vitro and in vivo, showed a remarkable heterogeneity in the immunostaining of ErbB2, ranging from very faintly to strongly stained. On the other hand, in both humans and hamsters, a consistently strong immunostaining was found in the Langerhans' islets, in the ganglia of intrapancreatic and extrapancreatic nerves, as well as in the CNS, spinal cord and adrenal gland. CONCLUSIONS: ErbB2 appears to play an important role in neuroendocrine tissues and is probably involved in the development and functional regulation of these cells. The concomitant expression of these factors and islet cell hormones very likely results in the activation of multiple growth-promoting pathways in pancreatic cancer and its aggressive behavior.     

Direct Determination of Red Cell Bound Antibody Specificity

S ummary . A new method is described for direct determination of specificity of red cell-bound antibodies without the need for antibody elution. This method employs Polybrene in an Auto Analyzer continuous flow system. Washed antibody-coated cells are mixed, in different proportions, with uncoated indicator cells of known blood type. If the indicator cells possess appropriate receptor sites for the cell-bound antibody, 'coagglutination' occurs between the antibody-coated and indicator cells. In contrast, in the absence of specific receptor sites, indicator cells not only fail to coagglutinate but physically interfere with the expected agglutination of antibodycarrying cells. Quantitative data are provided which appear to be related to the amount of cell-bound antibody. The technique has been used to identify antibodies with Rh and penicillin specificities and antibodies associated with acquired haemolytic anaemia.     

Esophageal motility in an adult with a congenital H-type tracheoesophageal fistula

Congenital H-type tracheoesophageal fistulas (TEF) are rare. Long-standing respiratory symptoms are the most common presenting complaints. Patients with these fistulas have a congenital esophageal motor abnormality characterized by uncoordinated, low-amplitude peristalsis of the esophagal body; both low and normal lower esophageal sphincter pressures have been described. These findings persist despite fistula repair. A case history of an adult patient with congenital TEF is presented and the literature is reviewed. This patient is unusual in that esophageal symptoms (dysphagia) were more prominent than the usual respiratory symptoms.     

Cancer of the pancreas in two brothers and one sister

Summary Over the past decades, pancreatic cancer has emerged as one of the most important malignancies in humans. This disease assumes a position of growing importance in view of its rising incidence and poor prognosis. Some familial pancreatic cancer has been reported with suggestions of hereditary, nutritional, home and familial environmental risk factors, and the possible role of genes in the development of this cancer among the members of one family. In an on-going case-control study of diet and cancer of the pancreas in Montreal, so far we were able to identify several familial cases of cancer of the pancreas. The most interesting case is the occurrence of this disease in two brothers and one sister all in their seventh decade of life. There was no history of pancreatitis among the cases or their relatives. Data from this study suggest that a familial predisposition to pancreatic cancer may occur in later decades of life. The role of genetic and environmental factors such as home remedies, familial food habits, etc., in the etiology of this cancer among these blood relatives, all in the same generation of one family, are unknown.     

Degeneration of the cerebellar dentate nucleus and the inferior olivary nuclei in HIV-1-infected brains: a morphometric analysis

Motor dysfunction is frequently noted in human immunodeficiency virus type 1 (HIV-1)-infected patients. Until recently, neuropathological changes found in the basal ganglia were advanced as pathogenetic mechanisms. In the present study, further brain structures involved in motor control were analyzed morphometrically. The volume density, numerical density, and the size of neurons in the cerebellar dentate nucleus and in both inferior olivary nuclei were determined. In both regions of HIV-1-infected brains, a significant reduction in the volume density, the numerical density of neurons and neuronal size was apparent. The morphometric data from the present study disclose involvement of both types of nuclei investigated during the course of HIV-1 infection, and might constitute a possible morphological substrate for the motor dysfunction seen in HIV-1-infected patients. Received: 22 February 1995 / Revised: 15 December 1995 / Accepted: 26 February 1996     

Effect of oral calcitriol pulse therapy on the lipid, calcium, and glucose homeostasis of hemodialysis-patients: its safety in a combination with oral calcium carbonate.

OBJECTIVE: To more clearly elucidate the conflicting results that have been obtained after oral calcitriol pulse therapy on lipid, glucose, and calcium levels in hemodialysis (HD) patients, and to determine safety of oral calcitriol pulse therapy in a combination with calcium carbonate. DESIGN: A randomized, crossover, placebo-controlled study. SETTING: HD centers in 3 teaching university hospitals. PATIENTS: Forty-eight chronic HD patients. METHODS: HD patients were randomized into 2 groups. Each group (n = 24), in addition to 4.5 g calcium carbonate daily, received either oral calcitriol pulse therapy or placebo twice weekly at the end of HD, sessions for 3 months, after which the 2 therapeutic groups were crossed-over, and for an additional 3 months, the calcitriol group received placebo, and the placebo group was put on calcitriol. Serum triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), total calcium, alkaline phosphatase, proteins, phosphorus, parathyroid hormone (PTH), blood pH, and glucose were measured at random and at the end of 3 and 6 months of the trial. RESULTS: After calcitriol therapy, triglyceride, serum PTH, total alkaline phosphatase, and fasting blood sugar significantly decreased, but total serum calcium significantly increased, whereas other examined parameters remained unchanged compared with the other groups. Calcium, phosphorus, calcium x phosphorus product, PTH levels, and all of these parameters were optimized in 18 (37.5%), 22 (45.8%), 34 (70.8%), 30 (62.5%), and 12 (%25) cases, respectively, in the calcitriol groups. No significant side effect was seen during the trial. CONCLUSION: Our findings indicate that short-term oral calcitriol pulse therapy in combination with calcium carbonate is safe and beneficial for metabolic abnormalities of HD patients; however, its safety for prolonged therapy is yet to be proved.     

Altered expression of the human retinoblastoma gene in monocytic leukaemias

Summary. Inactivation of the retinoblastoma growth suppressor gene (RB) is responsible for the development of retinoblastomas and occurs frequently in osteosarcomas and small cell lung carcinoma. Knowledge about the involvement of RB in the pathogenesis of myeloid leukaemias is still scarce. In this study we looked at the expression of the retinoblastoma gene product (p105) in 20 primary myelomonocytic and monoblastic leukaemias by Western blotting and immunocytochemistry using the anti-p105-monoclonal antibody PMG3-245. We found absence of or barely detectable levels of p105 in 11 patients (55%). Absence of or low levels of p105 were correlated with a higher leucocyte count at presentation (133 × 10⁹/l v 83 × 10⁹/l) and with the occurrence of extramedullary leukaemia (8/10 v 2/10). We conclude that abnormal expression of RB with absence of p105 or strongly reduced p105 levels occurs frequently in myelomonocytic and monoblastic leukaemias and that this may be correlated with a more malignant course of the disease.     

Malignancy is the Most Common Cause of Gastric Outlet Obstruction in the Era of H2 Blockers

Objectives: To determine the relative incidence of malignant and nonmalignant pathology in patients presenting with gastric outlet obstruction in the era of H2 blockers and to determine whether clinical features can differentiate between the two causes.
Methods: The charts of 33 consecutive patients with gastric outlet obstruction admitted to one institution between July 1990 and November 1993 were reviewed to determine etiology, management, and outcome. The diagnosis of gastric outlet obstruction was based on clinical presentation, an upper gastrointestinal barium study, and/or an inability during upper endoscopy to intubate the second portion of the duodenum. Patients with gastroparesis or a previously known cancer were excluded.
Results: Sixty-one percent (20 patients) had malignancy as the cause of their gastric outlet obstruction. Thirty-nine percent (13 patients) had benign disease. The patients with cancer tended to be older, and fewer had a history of peptic ulcer disease, although these factors were not statistically significant. The use of nonsteroidal anti-inflammatory drugs was not associated with gastric outlet obstruction. Four patients had malignancy that had not been suspected before operation despite numerous endoscopic and radiological studies.
Conclusion: The incidence of malignancy in patients presenting with gastric outlet obstruction is greater than 50%. The etiology of gastric outlet obstruction cannot be predicted by age, history of peptic ulcer disease, or nonsteroidal anti-inflammatory drug use. The endoscopic treatment of gastric outlet obstruction should be approached with caution because malignancy cannot be reliably excluded by endoscopic or radiological studies.