Ethanol diffusion miscalculation.
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Biomedical subjects
Publications and source records attributed to B McGregor.
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Extensive damage is thought to occur to endothelial cells in renal vasculitis and other glomerulopathies. The state of inflammation of these endothelial cells was investigated through the use of a panel of monoclonal antibodies (MAb) directed against thrombospondin (TSP), von Willebrand factor (vWF), integrins (alpha IIb beta 3, alpha v beta 3), CD36, and classical markers of inflammation (P-selectin, E-selectin, ICAM-1, VCAM). Results show that the anti-TSP MAb (LYP10) stains large areas of interstitium in focal sclerosis, vasculitis, membranous glomerulonephritis (GN), and diabetic GN but does not in normal kidney. In contrast, very limited areas are stained by LYP10 in minimal change nephropathy and Berger's disease. On paraffin-embedded specimens these areas stained by LYP10 appear edematous and early fibrous. Up-regulation of vWF and ICAM-1 is matched by an increased binding of LYP10 to the interstitium. In addition, fibrous crescents in injured glomeruli are stained by LYP10. This study reports for the first time an increased TSP secretion in glomerulopathies. Such TSP secretion may be part of physiological adaptive changes associated with inflammation and early fibrosis.
BACKGROUND: Nitric oxide and an apamin-sensitive transmitter may both contribute to neural inhibition in the human colon. The present study investigated the role of NO in regulating spontaneous rhythmic contractions and examined NO-dependent and independent components of neurally evoked hyperpolarization in the human colon. METHODS: Mechanical and electrical activity were recorded from isolated circular muscle strips. RESULTS: Rhythmic contractions were inhibited by nerve stimulation. This response was reduced by apamin, oxyhemoglobin, and L-NG-nitro arginine methyl ester (L-NAME). Electrical recording revealed two components of neurally evoked hyperpolarization: a fast hyperpolarization resulting from a single stimulus and a sustained hyperpolarization that developed with repetitive stimulation. Fast hyperpolarization was not affected by L-NAME or oxyhemoglobin but was significantly reduced by apamin. The sustained hyperpolarization was reduced by L-NAME or apamin. Exogenous NO and the P2y receptor agonist 2-methylthio adenosine 5'-triphosphate (2-MATP) inhibited spontaneous contractions and produced hyperpolarization. Apamin reduced the effects of 2-MATP but not those of NO. CONCLUSIONS: The results support the concept that the inhibitory neurotransmission in the human colon involves two transmitters. A single stimulus results in an apamin-sensitive response. With multiple stimuli, a NO-dependent response develops and sums with the apamin-sensitive mechanism, producing sustained hyperpolarization and inhibition of contractions.
The human papillomavirus (HPV) has been shown to be associated with neoplasms of the human colon using immunohistochemistry and in situ hybridization. We now report our use of the polymerase chain reaction and Southern blotting to investigate that same association. We selected 38 carcinomas, 21 adenomas, and 24 normal mucosal samples for the current study. Tissue sections were prepared, and then DNA was extracted and subjected to 40 cycles of amplification using Thermus aquaticus DNA polymerase and a set of degenerate primers. Amplified products were analyzed by agarose gel electrophoresis and Southern blotting. The L1 region of the HPV genome was identified in 13 of 38 carcinomas (32%), 8 of 21 adenomas (38%), and 2 of 24 normal biopsy specimens (8%). These observations validate our previous results and confirm the presence of HPV in human colon mucosa and tumors of that mucosa.
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Gold therapy is responsible for many neurological complications. We report a case presenting with the clinical and electrophysiological characteristics of neuromyotonia, polyradiculoneuritis and Morvan's fibrillary chorea. The various neurological complications of gold therapy and the possible relationships between these different syndromes are discussed.
The major histocompatibility complex (MHC) class I (HLA-A, B, C) and class II (HLA-DR) antigens are involved in cell-to-cell recognition and in regulating the immune response. Others have shown previously that MHC class I and class II antigens may be absent in a subset of malignant lymphomas, prompting the hypothesis that the absence of MHC antigen expression may be one of the mechanisms involved in the growth and dissemination of malignant lymphomas (by allowing a neoplasm to escape immune surveillance). To address this hypothesis, we analyzed MHC class I and class II (HLA-DR) antigen expression by diffuse large cell and large cell immunoblastic lymphomas in 88 and 117 patients, respectively, using frozen sections and the monoclonal antibodies W6/32 (HLA-A, B, C), anti-beta 2-microglobulin, and L203 (HLA-DR). Although there were no statistically significant clinical differences by MHC class II antigen expression, a small group of patients with MHC class I antigen-negative lymphomas were significantly younger (P = 0.03), less often had small neoplasms (P = 0.03), and were treated with doxorubicin-based chemotherapy more frequently (P = 0.04) than those with antigen-positive lymphomas. However, neither MHC class I nor class II antigen expression by the lymphomas consistently correlated with patient survival or freedom from relapse. This lack of correlation was true for all patients assessed, as well as for the subsets of patients with B-cell lymphomas, T-cell neoplasms, or those treated with doxorubicin-based chemotherapy. In accordance with previously published studies, stage, presence of B symptoms, and treatment with doxorubicin-based chemotherapy were of prognostic importance in univariate or multivariate analyses for survival or freedom from relapse. The findings may be considered evidence against the hypothesis that the absence of MHC class I or II antigen expression by malignant lymphomas plays a role in their tumorigenicity. However, we cannot completely exclude the possibility that the therapies used for this group of patients may have obscured any effect that MHC antigen expression exerts on prognosis.
We report a new case of successful liver transplantation in a 36-year-old patient with terminal hepatic failure due to erythropoietic protoporphyria. Data regarding protoporphyrin levels in erythrocytes and feces, before and after transplantation, seem to indicate that in this case protoporphyrin overproduction was in part due to liver synthesis. Four years after surgery, the patient is completely free of skin photosensitivity. His liver function tests are normal; there are no visible protoporphyrin deposits or ultrastructural abnormalities in his new liver. However, recurrence of the disease in the long term cannot be excluded, since erythrocyte protoporphyrin levels remained elevated after liver transplantation.
Human papillomavirus has been shown to be associated with squamous carcinomas. We evaluated benign and malignant colon tissues for the presence of human papillomavirus infection to determine if a similar relationship exists between human papillomavirus and colon neoplasms. Colon tissues were screened using an immunohistochemical technique to detect human papillomavirus antigen. In situ DNA hybridization was then performed on those tissues that yielded positive results by immunohistochemistry. Groups were compared using chi 2 analysis. Human papillomavirus antigen was present in 23% of normal colon specimens, 60% of benign tumors, and 97% of carcinomas. Human papilloma viral genome was demonstrated in 27% of benign tumors and in nearly 43% of all carcinomas tested. These data indicate that human papillomavirus infects the columnar mucosa of the colon, and that an association exists between human papillomavirus and colon neoplasia.
The presence of human papilloma virus (HPV) has recently been demonstrated in colon tumors, but the incidence of HPV infection in normal colon mucosa or in benign or malignant neoplasms of the mucosa is unknown. We studied both neoplastic and normal human colon tissue for the presence of HPV antigen using immunohistochemical techniques. Ninety colon specimens were studied. Three consecutive series of normal colon mucosa (N = 30), single benign tubulovillous adenomas (N = 30), and invasive carcinomas (N = 30) were selected and confirmed histologically. Formalin-fixed paraffin-embedded samples of each tissue were prepared using immunohistochemical techniques and resultant slides were read blindly and graded simply as positive or negative for HPV antigen. The presence of HPV antigen varied dramatically between groups, with 97% of the invasive carcinomas, 60% of the benign tubulovillous adenomas, and 23% of the normal mucosa positive for HPV antigen. Groups were statistically significant using chi 2 analysis (P less than 0.001). We conclude that an association exists between the human colon neoplasia and the presence of HPV antigen. This may suggest an etiologic role of the virus in colon cancer.
Ethanol inhibits the electrical and mechanical activities of gastric smooth muscle, but only at concentrations higher than can be provided by serum delivery. We speculated that the ethanol concentration in the gastric wall may exceed plasma levels by direct diffusion across the mucosa and through the muscle layers. A model of acute ethanol ingestion was created by partitioning the stomachs of three dogs with a surgical stapling device and instilling carbon 14 (14C)-labeled ethanol into the proximal segments. The flux of ethanol was traced by counting 14C in serial sections of the gastric wall. A mucosa-to-serosa gradient of 14C activity was established. The data indicate that direct diffusion from the mucosal surface will produce dramatically higher concentrations of ethanol in gastric muscle than would be anticipated from serum levels alone.
Nonpathological segments of muscle-stripped left colon from patients undergoing surgery for carcinoma, diverticulitis, or other causes were set up in flux chambers in order to determine the influence of intrinsic neurons on ion transport. In the basal state, both sodium and chloride were actively absorbed, and there was no significant residual ion flux. Electrical field stimulation of the intrinsic mucosal innervation evoked an increase in short-circuit current that was dependent on stimulus frequency and strength. The response was mimicked by scorpion venom, which is known to depolarize neurons, and was nearly abolished by tetrodotoxin, which prevents neurotransmitter release. Atropine reduced, but did not abolish, the response to neural stimulation. Carbachol, aminophylline, and theophylline significantly increased short-circuit current above basal levels. Electrical field stimulation evoked an increase in short-circuit current that could be accounted for by a decrease in net chloride absorption without any significant effect on sodium absorption or residual ion flux. These results suggest that ion transport in the human left colon is regulated by intrinsic submucosal cholinergic neurons as well as other neuronal types, and activation of these nerves could provide the basis for certain diarrheal disorders.
Controversy exists concerning the association of inguinal hernia and colonic carcinoma and, more specifically, whether the development of an inguinal hernia justifies sigmoidoscopy. To study the role of endoscopic screening in cases of inguinal hernia, we prospectively evaluated 464 patients with inguinal hernia over a 54-month period with flexible sigmoidoscopy. Each patient was over the age of 40 and male. Sigmoidoscopy documented polyps (97 patients, 21 percent) and carcinoma (22 patients, 5 percent). Multiple neoplasms were observed in 6 percent (7 of 119 patients). Occult blood was detected in the fecal specimens of 8 percent of the total group of patients, but in only 13 percent of the patients with polyps or carcinomas. A normal examination occurred in only 38 percent of the total group. By using the presence of an inguinal hernia in patients older than 40 years of age as an indication for sigmoidoscopy, we found that more than one of every four patients had an asymptomatic, concurrent malignant or premalignant colonic lesion. Flexible sigmoidoscopy should be used for screening colonic neoplasms in patients with inguinal hernia.
To determine optimal fluid management after elective aortic surgery we compared postoperative administration of 5% dextrose Ringer's lactate solution (102 patients) with 5% dextrose half-normal saline solution (80 patients). For 72 hours after operation, intravenous fluids were titrated to maintain urine output between 50 and 100 ml/hr. The group receiving 5% dextrose Ringer's lactate required less intravenous volume per day (2005 +/- 138 ml [mean +/- standard error of the mean] vs. 2701 +/- 145 ml, p less than 0.05), gained less weight (0.8 +/- 0.2 kg vs. 3.2 +/- 0.2 kg, p less than 0.05), and sustained less hyponatremia (serum sodium reduction, 0.1 mEq/L vs. 4.5 mEq/L, p less than 0.05). The group receiving 5% dextrose Ringer's lactate exhibited consistently lower pulmonary capillary wedge pressure (7.3 +/- 1.0 mm Hg vs. 11.4 +/- 1.9 mm Hg) and required treatment for fluid overload in 9 of 102 instances compared with 30 of 80 instances with hypotonic saline solution (p less than 0.05). The patients receiving 5% dextrose Ringer's lactate maintained higher arterial PO2 at 40% forced inspiratory oxygen (PaO2, 83 +/- 3 torr vs. PaO2, 67 +/- 5 torr, p less than 0.05). Optimal fluid management was approached by the use of 5% dextrose Ringer's lactate solution postoperatively. The use of hypotonic saline solution after aortic surgery offered no advantage and predisposed the patient to volume overload.
The correlation between age and CSF protein in 38 patients with pathologically proven motor neurone disease was the reverse of that described for normal subjects by Tibbling et al in 1977. Eight had CSF protein ranging from 0.75 g/1 to 1.52 g/L. These patients were younger, but other clinical and gross and light microscopy pathological features were not significantly different from those with lower CSF protein. Transudation from serum may be only one of the mechanisms underlying this elevation in CSF protein.
A case of localized ureteric stricture in a woman with analgesic nephropathy is reported. The problems of diagnosis and management are briefly discussed.
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Fifty new cases of carcinoma of the prostate were assessed prior to treatment to determine the incidence of bony metastases. The radioisotope bone scan was the most sensitive method of detecting metastases and of localising them. It was twice as accurate as the serum acid phosphatase estimation. Skeletal X-rays were the least accurate method. Forty-six per cent of patients had abnormal bone scans at presentation. The histological grade of the tumour correlated well with the bone scan. The higher the grade, the more likely was the bone scan to be abnormal. There is need for greater accuracy in detecting metastases, and the bone marrow acid phosphatase estimation, either alone or in conjunction with the bone scan, may provide this accuracy.