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Biomedical subjects

M J O'Brien

Publications and source records attributed to M J O'Brien.

At least 91 records · Page 5Linked to original sources

Signet ring carcinoma of the pancreas, a rare variant with very high CEA values. Immunohistologic comparison with adenocarcinoma.

Signet ring carcinoma of the pancreas is rare. We report a case which was remarkable for (1) diffuse, infiltrating growth which suggested chronic pancreatitis at laparotomy, and (2) an associated very high circulating carcinoembryonic antigen (CEA) level of 6400 ng/ml. The case report and autopsy are presented. Twelve other cases of pancreatic adenocarcinoma (non-signet ring) are compared with the signet ring carcinoma with respect to CEA staining and circulating levels. We conclude immunocytochemical staining of biopsy tissue for CEA is a useful adjunct in the interpretation of circulating CEA levels in pancreatic carcinoma.

Adenocarcinoma↗

Hepatocellular carcinoma: uptake of 99mTc-IDA in primary tumor and metastasis.

Four consecutive cases of proven hepatocellular carcinoma (HCC) showed significant avidity of 99mTc -labeled iminodiacetic acids (Tc- IDAs ) in preoperative scintigraphy. In one patient, the pulmonary metastasis showed uptake of Tc-IDA. Such scintigraphic findings were obvious only in the delayed scans, performed 2 1/2-4 hr after injection. Since Tc- IDAs and bilirubin are functional analogs physiologically, the ability of HCC to concentrate Tc- IDAs may be related to the ability of HCC neoplastic cells to form bile intracellularly. This hypothesis is supported by the fact that intracellular bile granules were found in the tumor cells of all four patients. This suggests a potential for using Tc- IDAs for the specific and preoperative diagnostic of HCC.

Adult↗

Immunocytochemical staining for CEA in small cell carcinoma of lung predicts clinical usefulness of the plasma assay.

Recent studies have shown plasma CEA levels are useful in both staging and monitoring response to treatment in patients with small cell cancer of the lung (SCCL). CEA elevations do not occur in all patients however, and have been of less value in patients with limited disease. Immunoperoxidase staining for CEA performed on tumor tissue from 48 patients (17 extensive, 31 limited disease) with SCCL revealed: (1) A strong correlation between positive CEA tissue staining and plasma CEA elevation. Plasma CEA elevations occurred in 18/21 CEA tissue positive patients and correlated with the clinical course in all 18. In contrast elevated plasma CEAs were seen in only 3/27 CEA tissue negative patients; (2) CEA tissue positive patients had a higher incidence of extensive disease (62% versus 18%) and a higher incidence of liver metastases (43% versus 7%); and (3) No correlation between histologic subtype and CEA tissue staining was apparent.

Carcinoembryonic Antigen↗

Psammomatous somatostatinomas of the duodenum.

The presence of psammoma bodies in carcinoid tumors of the gastrointestinal tract is a rare occurrence; it has also been reported to be associated with features of somatostatin production by the tumor cells. The morphologic features of three such tumors arising in the duodenum were studied by a combination of histochemical, immunocytochemical, and ultrastructural techniques in an effort to delineate their secretory profile and further subclassify them. All tumors showed a mixed architectural pattern with prominent areas of glandular differentiation. The psammoma bodies were almost exclusively located within the glandular lumina. In each instance, the majority of tumor cells showed histochemical and immunocytochemical features of somatostatin-containing cells, and one tumor studied ultrastructurally showed numerous large- and small-sized intracytoplasmic secretory granules, both of which contained somatostatin. In contrast to other endocrine tumors of the duodenum that frequently have a multihormonal secretory profile, psammomatous duodenal carcinoids are associated with the exclusive presence of somatostatin within tumor cells. While many more of such examples of this uncommon tumor need to be systematically investigated for their immunocytochemical and ultrastructural characteristics, duodenal somatostatinomas need to be included in the differential diagnosis of psammomatous tumors.

Adenoma, Islet Cell↗

Circulating CEA levels in patients with fulminant hepatitis.

CEA levels were determined in blood specimens from 14 persons suffering from fulminant hepatitis. Values ranged from 1.9 to 21 ng/ml with a mean of 7.0 ng/ml. All except one patient had a CEA level greater than 2.5 ng/ml, but only three exceeded 10 ng/ml. There was no correlation between single CEA levels and prognosis, routine liver chemistries, or histopathologic characterization of hepatic tissue obtained at postmortem examination. These data show that patients with fulminant hepatitis commonly had increased circulating levels of CEA, but these elevations were far less than may be found in patients with hepatic metastases. In severe hepatic dysfunction reduced hepatic clearance of CEA may be responsible for the increased levels.

Adolescent↗

Correlation of Plasma CEA and CEA tissue staining in poorly differentiated colorectal cancer.

A review of patients operated on for colorectal cancer disclosed poorly differentiated histologies in those whose preoperative and postoperative carcinoembryonic antigen (CEA) levels were no elevated, even in the presence of metastatic disease. CEA was therefore, of little prognostic value or predictive of disease recurrence in these patients. The amount of CEA in tumor tissue of 17 patients with poorly differentiated colorectal cancer was estimated with the immunoperoxidase staining technique and was correlated with histology and plasma CEA levels obtained during various stages of disease. Five tumors did not stain negatively for CEA and all had predominantly poorly differentiated histologies. In all of these patients metastatic disease developed but not elevated plasma CEA levels. In contrast 12 tumors stained positively for CEA and were found to contain either differentiated areas or signet ring cells. Serial plasma CEA levels correctly monitored the postoperative course of all 12 patients. Six of these had a relapse and all were detected by serial increases in plasma CEA. The remaining six were disease free greater than 48 months after resection and had normal plasma CEA levels. Among poorly differentiated tumors, those that contain glandforming areas or signet ring cells can be assumed to produce CEA and plasma CEA levels can be used effectively for monitoring. On the other hand, undifferentiated tumors which do not stain for CEA identify those patients whose plasma CEA levels do not provide a useful monitor.

Adenocarcinoma↗

Immunocytochemical localization of carcinoembryonic antigen in benign and malignant colorectal tissues. Assessment of diagnostic value.

Immunoperoxidase and immunofluorescence staining for carcinoembryonic antigen (CEA) was performed on paraffin and frozen sections, respectively, of colonic carcinomas (70), liver and lymph node metastases (20), mesenteric nodes (150), mucosa adjacent to carcinoma (40), colonic resection margins (20), normal colon (ten), and colorectal polyps (64) in order to assess its potential diagnostic value. On the basis of this study of the immunocytochemical localization of CEA in colorectal tissues, conclusions were as follows. (1) Localization of CEA to glycocalyx of surface epithelial cells is a normal finding in the colon and is similar in normal colon and mucosa distant and adjacent to infiltrating carcinoma. (2) Although strongly positive cell surface and intraluminal staining frequently correlates with the presence of carcinoma in neoplastic polyps, it is not by itself a reliable diagnostic criterion. (3) Failure to demonstrate CEA in a gland-forming carcinoma makes a diagnosis of colorectal carcinoma unlikely. (4) Poorly differentiated colorectal carcinoma usually contains much less demonstrable surface CEA, but may occasionally stain cytoplasm strongly. (5) Although lymph node micrometastases from colorectal carcinoma are readily demonstrated by immunoperoxidase staining for CEA, screening of hematoxylin and eosin-stained sections by a competent pathologist appears to be adequate for their detection.

Carcinoembryonic Antigen↗

Inhibition of in vitro production of aldosterone by manic-depressive sera.

Serum samples from psychiatric patients were added to incubations of rat adrenal cortical cells synthesizing aldosterone. A high proportion of sera from patients with bipolar manic-depressive psychosis inhibited aldosterone production, but chronic in-patients without affective disorders gave few inhibitory sera. Inhibition was greatest in depression, lowest during normal affect. In one patient studied through 11 affective cycles the inhibitor score increased during transitions from mania to depression, showing a significant regression on time. The possible relationship of this in vitro phenomenon to the defect of aldosterone regulation in manic-depressive psychosis is discussed.

Adrenal Cortex↗

Cholestasis and hepatic metastases: a factor contributing to extreme elevations of carcinoembryonic antigen.

Records of 19 autopsied patients with metastatic carcinoma were studied to elucidate the contribution to the elevation of antemortem plasma carcinoembryonic antigen (CEA) levels (range, 5.9--136,000 ng/ml) of 1) liver pathology and dysfunction, 2) tumor morphology and CEA content, and 3) tumor spread and location. Liver function tests and plasma CEA recorded within 8 weeks of death, autopsy records of tumor spread, liver weight (as an index of liver tumor mass), and histologic sections were reviewed. Tissue CEA was demonstrated in 15 patients by an immunoperoxidase method. Cholestasis was seen in histologic sections of tissue from 8 of 10 patients, and elevated bilirubin was seen in 7 of 10 patients with hepatic metastases and CEA levels greater than 1,000 ng/ml In contrast, histologically observed cholestasis and elevated bilirubin were seen in only 1 of 8 patients with CEA less than 500 ng/ml. A significant correlation was found between the plasma CEA level and histologically observed cholestasis (P less than 0.01). Serum bilirubin also correlated significantly (P less than 0.01), but alkaline phosphatase did not. Liver weight (tumor mass) showed a positive correlation with cholestasis (P less than 0.01) but not with circulating CEA. Markedly elevated plasma CEA levels (greater than 1,000 ng/ml) seen preterminally may partially reflect impaired excretion of CEA by the hepatobiliary system rather than, or in addition to, preterminal increase in CEA-producing tumor.

Bilirubin↗

Rat-brain pyruvate kinase: purification and effects of lithium.

Purified pyruvate kinase was prepared from pooled brains obtained from untreated rats. Its properties suggest that it is similar to type 'M' pyruvate kinase. Lithium inhibition was demonstrated at pharmacologically significant lithium concentrations (7%-12% at 2 mmol 1-1 Li) and this was similar in character to that previously seen in rabbit muscle pyruvate kinase, namely noncompetitive with respect to phosphoenol pyruvate, K+, and Mg2+ but competitive with ADP.

Animals↗

Inhibition of aldosterone production in adrenal cell suspensions by serum from patients with manic-depressive psychosis.

A method of preparing a suspension of cells of the zona glomerulosa from rat adrenal capsules treated with crude collagenase is described. The cells responded to ACTH, angiotensin II and serotonin by increased production of aldosterone. Pooled human sera or individual human sera (from healthy normal or non-psychiatric in-patients) to a final concentration of 30% had no effect on ACTH-stimulated production of aldosterone. Many serum samples from five patients with manic-depressive psychosis, however, caused a reduction in aldosterone production; 65% of those samples taken during depression, 44% of the samples taken during manic episodes and 23% of the samples taken when the mood was normal. Sera from manic-depressive patients also reduced the production of aldosterone caused by angiotensin II or serotonin. This effect of serum from manic-depressives in vitro may be related to the abnormalities of aldosterone control in such patients.

Adrenal Glands↗

Cefoxitin sodium compatibility with intravenous infusions and additives.

The compatibility and stability of cefoxitin sodium in solution with a series of frequently used intravenous infusion fluids and injectable additives were studied. Cefoxitin sodium's stability in various solutions was measured by ultraviolet spectrophotometry, iodometry, thin-layer chromatography, high-pressure liquid chromatography, ion-exchange chromatography and microbiological assay. Cefoxitin sodium was shown to maintain 90% of its initial concentration in aqueous solution for 40 hours at room temperature (25 C) and about 30 days at 5 C. The stability of cefoxitin sodium in common i.v. infusion fluids was independent of the concentrations (1 mg/ml to 400 mg/ml) and containers used, and was retained after 30 weeks storage at -20 C. Similar stability patterns were demonstrated for cefoxitin sodium in protein hydrolysate solutions and multivitamin formulations. Cefoxitin sodium was chemically and visually compatible with amikacin sulfate, gentamicin sulfate, kanamycin sulfate and tobramycin sulfate when admixed with normal saline or 5% dextrose in water injections. Cefoxitin sodium (397 mg/ml) in 0.5% lidocaine hydrochloride was stable after 26 weeks of storage at -20 C. Sodium cefoxitin is compatible with a wide variety of commonly used infusion solutions. Its stability is independent of concentration or pH within the ranges studied, and of types of common containers.

Aminoglycosides↗

Glyceraldehyde-3-phosphate dehydrogenase of Scenedesmus obliquus. Effects of dithiothreitol and nucleotide on coenzyme specificity.

NADH-dependent glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.--) of the photosynthetic alga Scenedesmus obliquus is converted to an NADPH specific form by incubation with dithiothreitol. The change in nucleotide specificity is accompanied by a reduction in the molecular weight of the enzyme from 550 000 to 140 000. Prolonged incubation with dithiothreitol results in the further dissociation of the enzyme to an inactive 70 000 dalton species. The 140 000 dalton, NADPH-specific enzyme is stabilized against dissociation and inactivation by the presence of NAD(H) or NADP(H). Optimum stimulation of NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase activity is achieved on incubation of the NADH-specific enzyme with dithiothreitol and NADPH, or dithiothreitol and a 1,3-diphosphoglycerate generating system. The relevance of these observations to in vivo light-induced changes in the nucleotide specificity of the enzyme is discussed.

Cyanobacteria↗

Respiratory muscle EMG in newborns: a non-intrusive method.

A non-intrusive method of recording the EMG of respiratory muscles with electronic suppression of the ECG artifact and averaging with a running window was employed in newborn infants at term to study respiratory patterns in different behavioural states. There are clear state-related differences in the diphragmatic and intercostal activity patterns. During most of the time in state 1 (quiet sleep) sustained tonic activity is found in the diaphragm as well as in intercostal muscles, but is virtually absent during state 2 (active sleep). During state 1 intercostal activity slightly precedes diaphragmatic activity whereas in state 2 both muscles contract about synchronously and vary widely in their amplitude. During periodic breathing the inspiratory EMG activity is absent in the pauses, but tonic activity may be present during periodic breathing in state 1. Isolated respiratory pauses with silence in the respiratory muscles occur in state 1 after sighs and starties with deep inspirations. During state 2 many respiratory pauses accompany gross movements and simultaneous laryngeal muscle activity suggests upper airway occlusion. Respiratory pauses without movements cannot be due to general alpha-motoneuron inhibition, because chin muscle activity may be seen at the same time. Gross movements often act as a reset mechanism for increase or decrease in tonic activity and phasic respiratory activity. Some speculations on the neural mechanisms of respiratory control based on the preliminary findings from the EMG recordings are mentioned.

Apnea↗