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Biomedical subjects

P Sagar

Publications and source records attributed to P Sagar.

At least 19 recordsLinked to original sources
PubMed1997

Anorectal melanoma--an incurable disease?

PURPOSE: This study was designed to describe recurrence and survival rates after operative treatment for anorectal melanoma and to identify predictive factors for recurrence. METHODS: Records of 50 patients with anorectal melanoma from 1939 to 1993 were reviewed. RESULTS: Overall five-year survival and disease-free survival were 22 and 16 percent, respectively. At the time of diagnosis, 26 percent of patients had metastatic disease, and all died within 12 (mean, 6.3) months. Five-year survival and recurrence rates were identical after either abdominoperineal resection (APR) or wide local excision, both with curative intent. Gender, size of tumor, presence of melanin, positive perirectal lymph nodes, or treatment were not predictive of recurrence. Anorectal melanoma was found incidentally after hemorrhoidectomy or polypectomy in five patients. Three other patients underwent an excisional biopsy of a lesion measuring less than 2 cm. Of these eight patients, five underwent APR and three underwent wide local excision with no microscopic residual tumor at pathology. All developed regional or systemic recurrence at a mean of 21 (range, 4-88) months, and all died of their disease at a mean of 29 (range, 5-98) months. CONCLUSION: Prognosis for anorectal melanoma is poor, irrespective of surgical treatment performed. No predictive factors for recurrence were identified in this series. Wide local excision with a negative margin of a least 1 cm is suggested as the treatment of choice. APR should be reserved for tumor not amenable to local excision or for palliative treatment of large obstructive lesion until effective adjuvant therapies are available.

Adult↗
PubMed1997

Pressure modulates monocyte migration.

Migration of monocytes into the subendothelial space of the aorta has been considered to be an important event in the development of atherosclerosis. Because hypertension is commonly associated with atherosclerosis, we studied the effect of applied pressure on the migration of monocytes. Direct applied pressure increased the migration (P < .001) of monocytes across a filter when compared with normal atmospheric pressure. The migration of monocytes was found to be directly related to the amount of the applied pressure. Amlodipine, a calcium channel blocker, attenuated the migration of monocytes under normal as well as increased pressure conditions in a dose-dependent manner. These studies provide a basis to speculate on the role of direct pressure in the migration of monocytes into the subendothelial space and the possibility that vasoactive agents may modulate the migration of monocytes independent of their pressure-lowering effect.

Amlodipine↗
PubMed1995

Risk-adjusted analysis of surgeon performance: a 1-year study.

A 1-year prospective analysis was undertaken of all non-day-case general surgery in a district general hospital. Using the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) scoring system 3004 patients were assessed. From the predictions of mortality and morbidity so obtained, a quality measure, the ratio of observed to expected numbers of deaths and complications (O:E ratio) was determined for each surgeon, both overall and within specialty zones. The present study demonstrates the serious hazard in using 'raw' uncorrected mortality and morbidity statistics to compare surgeon performance. Mortality rates varied from 1.0 to 4.9 per cent whereas O:E ratios ranged from 0.83 to 1.06; morbidity rates varied from 5.3 to 12.6 per cent with O:E ratios 0.86-1.02. Great misunderstanding may result from the publication of surgeon or hospital 'league tables'. The present study demonstrates a technique that might allow surgeon performance to be monitored adequately and accurately.

Day Care, Medical↗
PubMed1994

The prevalence of gut translocation in humans.

BACKGROUND/AIMS: Gut translocation of enteric organisms across the intact intestinal mucosa has been postulated as a potential source of sepsis in susceptible patients. However, little is known of its occurrence or significance in humans. The aim of this study was to determine the prevalence of gut translocation of bacteria in humans and attempt to identify any predisposing factors to its occurrence. METHODS: A consecutive series of 267 general surgical patients were examined for evidence of bacterial translocation by bacterial analysis of intestinal serosa and mesenteric lymph nodes taken at the time of surgery. RESULTS: Translocation occurred in 10.3% of patients overall. Both aerobic and anaerobic bacteria translocated. Excluding patients with distal intestinal obstruction and those with inflammatory bowel disease in whom translocation was more common, the prevalence was 5%. Neither jaundice, nutritional status, nor total parenteral nutrition predisposed to translocation. Similarly, mucosal atrophy did not predispose to this phenomenon. The development of postoperative septic complications was twice as common in patients with translocation as in those without, but mortality was unaffected. CONCLUSIONS: Translocation occurs as a spontaneous event in humans, but its clinical significance remains to be defined.

Bacterial Infections↗
PubMed1993

Prognostic value of p53 overexpression and c-Ki-ras gene mutations in colorectal cancer.

BACKGROUND: Mutations in Ki-ras codon 12 and the p53 gene are common abnormalities in colorectal cancer. The occurrence of p53 overexpression and/or Ki-ras codon 12 mutations were analyzed in 100 colorectal adenomas to determine if they were related to patient survival. METHODS: p53 overexpression was identified by immunohistochemistry, and Ki-ras codon 12 mutations were detected using the polymerase chain reaction and a restriction enzyme digestion method. RESULTS: p53 overexpression was identified in 45% of tumors, with a higher frequency identified in DNA aneuploid and left-sided tumors than in DNA diploid and right-sided tumors. Mutations in Ki-ras codon 12 were identified in 24% of carcinomas. Individually, mutations in Ki-ras codon 12 or p53 overexpression were not prognostic indicators of survival. However, a statistically significant difference in survival was identified when these two oncogenic abnormalities were analyzed together. The median survival of patients whose tumors contained both oncogenic abnormalities was less than half of that of patients with either alteration alone or without either abnormality. CONCLUSIONS: Screening for multiple genetic abnormalities in colorectal cancers excised at surgery may prove to be a useful tool in determining prognosis.

Adenocarcinoma↗
PubMed1993

p53 expression and K-ras mutation in colorectal adenomas.

The frequency of p53 overexpression and K-ras codon 12 mutation was investigated in a series of colorectal adenomas. p53 was detected by immunohistochemistry in only 5% of tumours, whereas K-ras mutation was found in eight of 30 adenomas examined. In vitro, mutant p53 and ras genes cooperate to transform primary rat cells into a tumourigenic cell line. The presence of both p53 overexpression and K-ras mutation in a benign tubulovillous polyp in the present series suggests that in vivo this combination of events is insufficient to cause malignant transformation of a large bowel adenoma.

Adenoma↗
PubMed1992

Aberrations in cerebral vascular functions due to Plasmodium yoelii nigeriensis infection in mice.

Plasmodium yoelii nigeriensis infection in mice caused an increase in uptake of 125I-labeled bovine serum albumin, 51Cr-labeled erythrocytes and Evans blue dye from peripheral circulation into the brain. Isolated cerebral microvessels which were characterized in terms of their morphology under scanning electron microscope and enhancement of the specific activities of biochemical markers, viz. alkaline phosphatase, gamma-glutamyl transpeptidase, and monoamine oxidase, showed significant decrease in these activities due to P. yoelii nigeriensis infection. On the other hand, relatively minor (statistically insignificant) changes occurred in the first two enzyme specific activities in the cerebral cortex and monoamine oxidase registered an increase in this tissue due to infection. Histological examination of the cerebral tissue of infected animals by light and electron microscopy showed broken blood vessel walls and leakage of erythrocytes into extravascular space, some of which contained intraerythrocytic malarial parasite in a state of cell division.

Alkaline Phosphatase↗
PubMed1992

Oxido-reductive functions of Entamoeba histolytica in relation to virulence.

Entamoeba histolytica can reduce nitro-blue tetrazolium (NBT) in Hank's balanced salt solution to almost the same extent as in Eagle's minimal medium. Further, this reduction was stimulated only to a minor degree by glucose, pyruvate and DL-serine, substrates known to support respiratory activity (O2 uptake) in E. histolytica. However, both NADH and NADPH increased NBT reduction several-fold, the effect being greater with NADPH. A sizeable proportion of this endogenous dye-reducing capability (in Hank's solution) was associated with low-speed sediments obtainable from amoebic homogenates, which also shared the bulk of 125I labelling (when the homogenates were prepared after surface labelling with Na 125I). Conversion of the dye to formazan was strongly inhibited by -SH blocking agents, but was not influenced by rotenone and antimycin A. The activity was also inhibited by H2O2, but stimulated by catalase. Superoxide dismutase only slightly curtailed NBT reduction in intact cells, but inhibited it in homogenates in a concentration-dependent manner to a maximal extent of 33%. Almost the same degree of curtailment of this activity was induced by anaerobic conditions. Both concanavalin A (Con A) and phorbol myristate acetate stimulated the activity in intact cells, though the effect of Con A was nullified by alpha-methyl mannoside. Both NBT-reducing capability and alcohol dehydrogenase activities were higher in the more virulent IP:106 strain, and they increased with time in cultures of NIH:200 in a cholesterol-enriched environment.

Alcohol Dehydrogenase↗
PubMed1992

Cerebral ammonia levels and enzyme changes during Plasmodium yoelii infection in mice.

Ammonia, lactate and glutamate levels and the activities of glutamine synthetase (GS), glutamate dehydrogenase (GDH), glutaminase (GLN), aspartate transaminase (AST), phosphofructokinase (PFK) and monoamine oxidase (MAO) were compared in the brain tissue of normal and P. yoelii infected mice. The brain lactate increased by 96% at peak parasitaemia. Cerebral ammonia also exhibited an increase in infected mice which was parasitaemia dependent, while glutamate remained almost unchanged. The brain glutamine synthetase registered an increase of 35% (P < 0.001) in post-mitochondrial fractions, this effect being perceptible even at low parasitaemia, but attained constancy at parasitaemia levels higher than 20%. The activity of monoamine oxidase and phosphofructokinase increased by 105% (P < 0.02) and 41% (P < 0.05) respectively while glutamate dehydrogenase decreased by 15% (P < 0.001). Glutaminase and aspartate transaminase were not significantly influenced by infection (tested only at high parasitaemia levels). It has been postulated that cerebral hypoxia and aberrations in ammonia metabolism may both contribute towards malaria induced cerebral complications.

Ammonia↗
PubMed1991

p53 in colorectal cancer: clinicopathological correlation and prognostic significance.

p53 protein was detected by immunohistochemistry in 42% of 52 colorectal adenocarcinomas. Positive tumours were significantly more frequent in the distal colon, and demonstrated a higher rate of cell proliferation. No correlation was found with tumour grade, Dukes' stage, presence of DNA aneuploidy or patient survival. The role of p53 in colorectal carcinogenesis is discussed with particular reference to differences between proximal and distal large bowel cancers.

Colorectal Neoplasms↗
PubMed1991

Biochemical and ultrastructural studies induced by phanquone on Entamoeba histolytica NIH-200.

The action of phanquone on the incorporation of (14C)1-DL-valine and (14C)-8-adenine in TCA insoluble fractions of Entamoeba histolytica was examined as indices of RNA and protein synthesis respectively. The former was found to show greater sensitivity to the drug in terms of the effect manifested in the dose response curves for these parameters. Electron microscopic investigations with increasing concentrations of the drug demonstrated progressive vacuolization with concomitant dissolution of ribosomal helices. The drug had no significant effect on nucleus and plasma membrane even at concentration as high as 200 micrograms/ml.

Amebicides↗
PubMed1990

Effect of Plasmodium yoelii infection on GABA metabolism of mouse brain.

Plasmodium yoelii infection in albino mice decreased the activity of brain glutamic acid decarboxylase (GAD) by about 30 and 48% in crude homogenate and its synaptosomal fraction, respectively. The decrease was evident from 20% parasitemia and remained more or less constant up to 80% parasitemia. The Km values of GAD in normal and infected animals were 1.2 x 10(-2) and 3.3 x 10(-2) mM, respectively, indicating a decrease in enzyme substrate affinity due to infection. The lowered GAD activity rose to slightly above normal by treatment of infected animals with chloroquine. Decrease in GAD activity reflected lower gamma-aminobutyric acid (GABA) levels in the infected brain; however, GABA-transaminase activity was not significantly influenced by infection. It has been proposed that impaired GABA synthesis may be due to hypoxia induced by malarial infection.

4-Aminobutyrate Transaminase↗
PubMed1990

Specific features of phosphomonoesterase of Entamoeba histolytica (NIH-200).

Axenically grown E. histolytica possess significant acid phosphatase activity. The Km of the enzyme was found to be 7.1 x 10(-3) and was maximally active at pH 4.5. Acid phosphatase activity was significantly inhibited by Cu2+, cysteine and was activated by tartrate and fluoride. It was found that E. histolytica acid phosphatase differs in some properties as compared to the enzyme reported from other sources.

Animals↗
PubMed1990

Action of metronidazole on Entamoeba histolytica: an ultrastructural study.

Metronidazole (19 micrograms/ml) caused progressive increase in vacuolization in Entamoeba histolytica cells with disintegration of its plasma membrane leading to almost complete disappearance of the latter within 3 hours. The drug also induced formation of helical ribosomal aggregates in the cytoplasm and disappearance of button like structures inside the nucleus.

Animals↗