Search PubMed⌕ Search

Biomedical subjects

N Weidner

Publications and source records attributed to N Weidner.

At least 145 records · Page 8Linked to original sources

Mucosal ganglioneuromatosis associated with multiple colonic polyps.

Two unusual cases of colonic ganglioneuromatosis are described. One case was associated with multiple adenomatous polyps in a 74-year-old man and the second case was associated with juvenile polyps in a 16-year-old boy. To our knowledge this is the first report of colonic mucosal ganglioneuromatosis associated with multiple adenomatous polyps and the second report associated with multiple juvenile polyps. In the first case the ganglioneuromatosis was found in colonic mucosa without adenomatous changes, while in the second case ganglioneuromatosis was found both within normal mucosa and within juvenile polyps. The relationship between mucosal ganglioneuromatosis and multiple colonic polyps remains unclear. Neither patient has yet developed features to suggest either multiple endocrine neoplasia type 2b or von Recklinghausen's disease.

Adolescent↗

Peptic ulceration with marked epithelial atypia following hepatic arterial infusion chemotherapy. A lesion initially misinterpreted as carcinoma.

Peptic ulceration is a known complication of hepatic arterial chemotherapy for metastatic disease. We report a case of peptic ulceration associated with marked epithelial atypia initially interpreted as carcinoma, probably metastatic in nature. Subsequent partial gastric resection proved the lesion benign. Examination of other gastric biopsies from ulcerated and nonulcerated mucosa from similarly treated patients has revealed similar marked atypical changes. The etiology of the epithelial atypia and ulceration remains unanswered, but is probably related to locally enhanced chemotherapeutic cytotoxicity or ischemia. Care should be taken not to interpret the marked epithelial atypia as carcinoma in this clinical setting.

Aged↗

Immunoglobulin-complexed aspartate aminotransferase.

We report two cases of unexplained, isolated, persistently increased aspartate aminotransferase activity in serum. In the first patient, this lasted for 10 years and prompted multiple hospitalizations and medical/surgical consultations. For patient two, the abnormal enzyme activity resulted in hospitalization for further evaluation of possible heart disease. In spite of extensive investigation to determine the possible reason for the abnormality, no clear clinical cause was ever discovered in either patient. Electrophoretic and immunologic evidence indicates that the enzyme was complexed to IgG in the serum of both individuals. Recognition that this complex is probably benign may obviate other patients having to undergo unnecessary hospitalization, anxiety, and expense.

Aspartate Aminotransferases↗

Laboratory diagnosis of acute myocardial infarct: usefulness of determination of lactate dehydrogenase (LDH)-1 level and of ratio of LDH-1 to total LDH.

Recent development of an antibody to the M subunit of lactic dehydrogenase (LDH) allows the rapid isolation and measurement of LDH-1 levels. I and my colleagues studied 101 consecutive patients admitted to the hospital for possible acute myocardial infarct (AMI). The LDH-1 level was 100 IU/L or more, and the ratio of LDH-1 to total LDH (LDH-1/LDH-T ratio) was 0.40 or higher, during the course of illness in 93% of the patients with AMI. The specificity was 95% and the positive predictive value, 86%. These two criteria were met eight to 24 hours after the appearance of symptoms, and often persisted seven to 14 days. Measurement of LDH-1 level and LDH-1/LDH-T ratio is a useful adjunct in the laboratory diagnosis of AMI.

Adult↗

The accuracy of Masson's trichrome stain in predicting the presence or absence of glomerular immune complexes.

The accuracy of Masson's trichrome stain to predict the presence of immune complexes was determined in 63 renal biopsies. When immunofluorescence was defined as the reference method, the histologic method correctly predicted the presence or absence of deposits in 70% of biopsy specimens, while electron microscopy was accurate in 79% of specimens. This difference was not statistically significant. The commonest error in our assessment of the Masson's trichrome-stained specimens was the erroneous interpretation of specimens showing minimal change nephropathy or ischemic glomerulopathy by immunofluorescence and electron microscopy. This resulted in a falsely positive diagnosis of one or another of the glomerulonephritides in 13% of cases. Thus, the routine study of renal biopsies with Masson's trichrome stain is clearly useful and should be applied with caution, but it does not replace electron-microscopic and immunofluorescence studies.

Adolescent↗

Adaptation of the EMIT theophylline assay to kinetic analyzers: the relationship of reaction kinetics to calculation procedures.

We investigated the kinetic characteristics of an enzyme immunoassay system (EMIT) for the determination of theophylline. Less than 10% of the glucose-6-phosphate and NAD+ are consumed and the glucose-6-P-dehydrogenase-theophylline complex is essentially saturated with these substrates during the course of the reaction. However, apparently as the result of antibody heterogeneity, the rate does change during the course of the reaction. As a result, the values of the kinetic parameters for the theophylline saturation curve vary with the timing interval chosen for measurement. We show that the values of these parameters govern the application of the available methods of calculating EMIT data, the graphical procedure suggested by the manufacturer, logit-log, log-log, and curve fitting. These studies (1) explain the basis of the graphical procedure and why it does not always provide proper calibration, (2) show that to appropriately understand the application of any of the calculation procedures one should determine the values of the kinetic constants of the theophylline saturation curve in the particular assay conditions, and (3) illustrate simple, practical procedures for determining the values of these constants for any instrument-EMIT assay system. Specific illustrations are shown for the EMIT theophylline system with two kinetic analyzers, the Abbott ABA-100 and Gilford 3500, with which markedly different reaction conditions are used.

Autoanalysis↗

A clinically applicable high-pressure liquid chromatographic method for measurement of serum theophylline, with detailed evaluation of interferences.

A high-pressure liquid chromatographic method for the routine measurement of serum theophylline that is accurate, specific, and sensitive is presented. It is technically simple, requires only 50 microliter serum, and takes relatively little technician time. Values for theophylline in sera obtained by this method correlate well with those obtained by use of a gas-liquid chromatographic method (r = 0.980) and with values obtained by the commonly used spectrophotometric method (r = 0.939) when the latter is free of interference. The assay has been employed for two years in a routine clinical chemistry laboratory, with interassay coefficients of variation of 2.4-3.2%. Interferences have been identified at an incidence rate of 3.8% of all specimens, and interfering substances include cephazolin, chloramphenicol, sulfamethoxazole, and sulfisoxazole. A calculation technic that allows a reliable and clinically useful estimation of a range of concentrations of theophylline in the serum when these interferences are present is described. In contrast, the incidence of interferences with the spectrophotometric method is 4.9%, and in this method the interferences prevent the analysis of theophylline. Of 33 samples having interferences by use of the spectrophotometric method, the high-pressure liquid chromatographic technic yielded precise values for theophylline in 21 and reliable estimates of ranges of concentrations of theophylline in the remaining 12.

Cefazolin↗

Assay of theophylline: comparison of EMIT on the ABA-100 to HPLC, GLC and UV procedures, with detailed evaluation of interferences.

The EMIT technique for theophylline measurement as adapted to the Abbott Bichromatic Analyzer (ABA-100), was compared to two other established procedures. EMIT results correlated well with those obtained with high pressure liquid chromatographic (HPLC) (r = 0.995, N = 54) and spectrophotometric (UV) (r = 0.95, N = 37) methods when the patient samples used were free of apparent interferences in the comparison methods. On samples exhibiting interferences with HPLC and/or UV methods, the EMIT assay gave the same results as a gas-liquid chromatographic procedure which showed no interferences. In addition, theophylline metabolites, xanthine analogs and many commonly administered drugs did not interfere with the EMIT theophylline assay. An interassay coefficient of variation of 3.5--6.5% was demonstrated. Our data indicate that the EMIT technique exhibits adequate precision and specificity for routine theophylline determinations. Unlike the HPLC or UV procedures, we have not encountered any interferences with the EMIT technique.

Chromatography, Gas↗

A high-pressure liquid chromatography method for serum quinidine and (3S)-3-hydroxyquinidine.

A bonded reversed phase, high pressure liquid chromatography (HPLC) method for serum quinidine and its major metabolite in serum, (3S)-3-hydroxyquinidine, is presented. The method employs toluene, rather than benzene for extraction of 100 microliter of serum, can utilize either absorbance or fluorescence detectors, and utilizes a column and equipment which is also suitable for theophylline analyses. Quinidine values in sera by the present method correlated well with fluorometric non-chromatographic methods using ethylene chloride (r = 0.932) or benzene-sulfuric acid (r = 0.950) for extraction of the quinidine. The comparison data suggest a therapeutic range for quinidine of 1.3--5.0 mg/liter when measured by HPLC. In over one year of routine use in a clinical chemistry laboratory, the method has proven to be rapid and precise with interassay coefficients of variation of 2.5--5.5%. No interferences with the HPLC method have yet been identified.

Chromatography, High Pressure Liquid↗

Effect of fibrin degradation products and thrombin on fibrinogen synthesis.

The effect of intravenous administration of homologous fibrin degradation products and thrombin on fibrinogen synthesis was assessed in rabbits. The relative fibrinogen synthesis rate was calculated as a ratio of the amount of radiolabelled lysine incorporated into fibrinogen to the amount incorporated into albumin during the same measurement period. An increase in this ratio above control would indicate a relatively specific stimulation of fibrinogen synthesis as compared with albumin, which is not an acute-phase reactant. Injection of 45 mg of 'early' or 'late' fibrin degradation products failed to produce a significant increase in the relative fibrinogen synthesis rate, suggesting that fibrin degradation products play no feedback role in controlling fibrinogen synthesis. Infusion of small amounts of homologous thrombin (15--25 NIH u) was followed by a small but statistically significant elevation of the relative fibrinogen synthesis rate. This was not accompanied by any increase in the levels of fibrinogen degradation products in plasma, or by any decrease in plasma fibrinogen concentration, possibly suggesting that thrombin can stimulate fibrinogen synthesis by a mechanism independent of significant fibrinogenolysis or intravascular coagulation.

Animals↗

Grafts of genetically modified Schwann cells to the spinal cord: survival, axon growth, and myelination.

Schwann cells naturally support axonal regeneration after injury in the peripheral nervous system, and have also shown a significant, albeit limited, ability to support axonal growth and remyelination after grafting to the central nervous system (CNS). It is possible that Schwann cell-induced axonal growth in the CNS could be substantially increased by genetic manipulation to secrete augmented amounts of neurotrophic factors. To test this hypothesis, cultured primary adult rat Schwann cells were genetically modified using retroviral vectors to produce and secrete high levels of human nerve growth factor (NGF). These cells were then grafted to the midthoracic spinal cords of adult rats. Findings were compared to animals that received grafts of nontransduced Schwann cells. Spinal cord lesions were not placed prior to grafting because the primary aim of this study was to examine features of grafted Schwann cell survival, growth, and effects on host axons. In vitro prior to grafting, Schwann cells secreted 1.5+/-0.1 ng human NGF/ml/10(6) cells/day. Schwann cell transplants readily survived for 2 wk to 1 yr after in vivo placement. Some NGF-transduced grafts slowly increased in size over time compared to nontransduced grafts; the latter remained stable in size. NGF-transduced transplants were densely penetrated by primary sensory nociceptive axons originating from the dorsolateral fasciculus of the spinal cord, whereas control grafts showed significantly fewer penetrating sensory axons. Over time, Schwann cell grafts also became penetrated by TH- and DBH-labeled axons of putative coerulospinal origin, unlike control cell grafts. Ultrastructurally, axons in both graft types were extensively myelinated by Schwann cells. Grafted animals showed no changes in gross locomotor function. In vivo expression of the human NGF transgene was demonstrated for periods of at least 6 m. These findings demonstrate that primary adult Schwann cells 1) can be transduced to secrete augmented levels of neurotrophic factors, 2) survive grafting to the CNS for prolonged time periods, 3) elicit robust growth of host neurotrophin-responsive axons, 4) myelinate CNS axons, and 5) express the transgene for prolonged time periods in vivo. Some grafts slowly enlarge over time, a feature that may be attributable to the propensity of Schwann cells to immortalize after multiple passages. Transduced Schwann cells merit further study as tools for promoting CNS regeneration.

Animals↗

Review and update: oncogenic osteomalacia-rickets.

Oncogenic or tumor-induced osteomalacia-rickets is a syndrome characterized by hypophosphatemia, renal phosphate wasting, and decreased serum 1,25-dihydroxyvitamin D3 levels. The tumors secrete a phosphaturic substance that causes total body phosphate depletion, leading to osteomalacia or rickets. Although the tumors are histologically polymorphous, personal review of 16 tumors documented to cause this syndrome revealed four morphologic patterns. The first contained 10 unique-appearing, mixed connective tissue tumors having variably prominent vessels, osteoclastlike giant cells, focal microcystic changes, dystrophic calcification, osseous metaplasia, and/or poorly developed cartilagelike areas. With one exception, all tumors of this group occurred in soft tissue and were benign. The single malignant tumor originated in bone, recurred locally, and metastasized to lung. The remaining tumors occurred in bone and showed benign clinical behavior. They resembled tumors known to occur in bone, that is osteoblastomalike (3 tumors), nonossifying fibromalike (2 tumors), and ossifying fibromalike (1 tumor).

Bone Neoplasms↗

Myoid gonadal stromal tumor with epithelial differentiation (? testicular myoepithelioma).

A 46-year-old man presented with a cytologically bland testicular tumor composed of spindle cells that showed both epitheliallike (ie, true desmosomes and tonofilamentlike structures) and myogenous differentiation (ie, thin filaments with focal densities and alpha-smooth muscle actin immunoreactivity). Tumor cells were immunoreactive for vimentin and S-100 protein but negative for cytokeratin and desmin. Peritubular myoid cells are present in the normal testis; contain subplasmalemmal micropinocytotic vesicles; show thin filaments with focal densities; and are reactive with desmin, vimentin, and alpha-smooth muscle actin. They have no desmosomes and lie outside the basement membrane of the seminiferous tubules; thus they are not true myoepithelial cells (a cell type not present in the testis). Paradoxically, the current tumor appeared to show bidirectional differentiation, mimicking both a peritubular myoid spindle cell and an epitheliallike cell (possibly similar to the granulosa cell or rete testis epithelial cell). Although the findings suggest myoepithelial differentiation, the cytogenesis of this tumor remains uncertain.

Actins↗

Atypical tumor of the mediastinum: epithelioid hemangioendothelioma containing metaplastic bone and osteoclastlike giant cells.

A 66-year-old woman presented with a superior-anterior mediastinal mass that contained considerable calcification by computed tomography. Initial biopsy interpretation was inconclusive but suggested a giant cell sarcoma of soft parts because the tumor contained atypical epithelioid cells and osteoclastlike giant cells. After radiation and chemotherapy, the tumor was removed. It contained large epithelioid cells, pale chondroid areas, metaplastic bone, and osteoclastlike giant cells. Immunohistochemical and electron microscopic studies revealed the epithelioid cells to be factor VIII positive and to contain abundant intermediate filaments, micropinocytotic vesicles, Weibel-Palade bodies, basal lamina, and primitive cell-cell junctions. These epithelioid cells also stained for muscle-specific actin (HHF-35), yet were negative for desmin and cytokeratins (CAM 5.2 and AE1/3). The findings were most consistent with those reported to occur in epithelioid hemangioendothelioma.

Actins↗